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2. Author Correction: Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
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Bailey M. H., Meyerson W. U., Dursi L. J., Wang L. -B., Dong G., Liang W. -W., Weerasinghe A., Li S., Li Y., Kelso S., Akbani R., Anur P., Buchanan A., Chiotti K., Covington K., Creason A., Ding L., Ellrott K., Fan Y., Foltz S., Getz G., Hale W., Haussler D., Hess J. M., Hutter C. M., Kandoth C., Kasaian K., Kasapi M., Larson D., Leshchiner I., Letaw J., Ma S., McLellan M. D., Men Y., Mills G. B., Niu B., Peto M., Radenbaugh A., Reynolds S. M., Saksena G., Sofia H., Stewart C., Struck A. J., Stuart J. M., Wang W., Weinstein J. N., Wheeler D. A., Wong C. K., Xi L., Ye K., Bieg M., Boutros P. C., Buchhalter I., Butler A. P., Chen K., Chong Z., Drechsel O., Jonathan Dursi L., Eils R., Espiritu S. M. G., Fulton R. S., Gao S., Gelpi J. L., Gerstein M. B., Gonzalez S., Gut I. G., Hach F., Heinold M. C., Hinton J., Hu T., Huang V., Huang Y., Hutter B., Jones D. R., Jung J., Jager N., Kim H. -L., Kleinheinz K., Kumar S., Kumar Y., Lalansingh C. M., Letunic I., Livitz D., Ma E. Z., Maruvka Y. E., Mashl R. J., Menzies A., Milovanovic A., Nielsen M. M., Ossowski S., Paramasivam N., Pedersen J. S., Perry M. D., Puiggros M., Raine K. M., Rheinbay E., Royo R., Sahinalp S. C., Sarrafi I., Schlesner M., Simpson J. T., Stebbings L., Stobbe M. D., Teague J. W., Tiao G., Torrents D., Wala J. A., Wang J., Waszak S. M., Weischenfeldt J., Wendl M. C., Werner J., Wu Z., Xue H., Yakneen S., Yamaguchi T. N., Yellapantula V. D., Yung C. K., Zhang J., Aaltonen L. A., Abascal F., Abeshouse A., Aburatani H., Adams D. J., Agrawal N., Ahn K. S., Ahn S. -M., Aikata H., Akdemir K. C., Al-Ahmadie H., Al-Sedairy S. T., Al-Shahrour F., Alawi M., Albert M., Aldape K., Alexandrov L. B., Ally A., Alsop K., Alvarez E. G., Amary F., Amin S. B., Aminou B., Ammerpohl O., Anderson M. J., Ang Y., Antonello D., Aparicio S., Appelbaum E. L., Arai Y., Aretz A., Arihiro K., Ariizumi S. -I., Armenia J., Arnould L., Asa S., Assenov Y., Atwal G., Aukema S., Auman J. T., Aure M. R., Awadalla P., Aymerich M., Bader G. D., Baez-Ortega A., Bailey P. J., Balasundaram M., Balu S., Bandopadhayay P., Banks R. E., Barbi S., Barbour A. P., Barenboim J., Barnholtz-Sloan J., Barr H., Barrera E., Bartlett J., Bartolome J., Bassi C., Bathe O. F., Baumhoer D., Bavi P., Baylin S. B., Bazant W., Beardsmore D., Beck T. A., Behjati S., Behren A., Bell C., Beltran S., Benz C., Berchuck A., Bergmann A. K., Bergstrom E. N., Berman B. P., Berney D. M., Bernhart S. H., Beroukhim R., Berrios M., Bersani S., Bertl J., Betancourt M., Bhandari V., Bhosle S. G., Biankin A. V., Bigner D., Binder H., Birney E., Birrer M., Biswas N. K., Bjerkehagen B., Bodenheimer T., Boice L., Bonizzato G., De Bono J. S., Boot A., Bootwalla M. S., Borg A., Borkhardt A., Boroevich K. A., Borozan I., Borst C., Bosenberg M., Bosio M., Boultwood J., Bourque G., Bova G. S., Bowen D. T., Bowlby R., Bowtell D. D. L., Boyault S., Boyce R., Boyd J., Brazma A., Brennan P., Brewer D. S., Brinkman A. B., Bristow R. G., Broaddus R. R., Brock J. E., Brock M., Broeks A., Brooks A. N., Brooks D., Brors B., Brunak S., Bruxner T. J. C., Bruzos A. L., Buchholz C., Bullman S., Burke H., Burkhardt B., Burns K. H., Busanovich J., Bustamante C. D., Butte A. J., Byrne N. J., Borresen-Dale A. -L., Caesar-Johnson S. J., Cafferkey A., Cahill D., Calabrese C., Caldas C., Calvo F., Camacho N., Campbell P. J., Campo E., Cantu C., Cao S., Carey T. E., Carlevaro-Fita J., Carlsen R., Cataldo I., Cazzola M., Cebon J., Cerfolio R., Chadwick D. E., Chakravarty D., Chalmers D., Chan C. W. Y., Chan K., Chan-Seng-Yue M., Chandan V. S., Chang D. K., Chanock S. J., Chantrill L. A., Chateigner A., Chatterjee N., Chayama K., Chen H. -W., Chen J., Chen Y., Chen Z., Cherniack A. D., Chien J., Chiew Y. -E., Chin S. -F., Cho J., Cho S., Choi J. K., Choi W., Chomienne C., Choo S. P., Chou A., Christ A. N., Christie E. L., Chuah E., Cibulskis C., Cibulskis K., Cingarlini S., Clapham P., Claviez A., Cleary S., Cloonan N., Cmero M., Collins C. C., Connor A. A., Cooke S. L., Cooper C. S., Cope L., Corbo V., Cordes M. G., Cordner S. M., Cortes-Ciriano I., Cowin P. A., Craft B., Craft D., Creighton C. J., Cun Y., Curley E., Cutcutache I., Czajka K., Czerniak B., Dagg R. A., Danilova L., Davi M. V., Davidson N. R., Davies H., Davis I. J., Davis-Dusenbery B. N., Dawson K. J., De La Vega F. M., De Paoli-Iseppi R., Defreitas T., Dei Tos A. P., Delaneau O., Demchok J. A., Demeulemeester J., Demidov G. M., Demircioglu D., Dennis N. M., Denroche R. E., Dentro S. C., Desai N., Deshpande V., Deshwar A. G., Desmedt C., Deu-Pons J., Dhalla N., Dhani N. C., Dhingra P., Dhir R., DiBiase A., Diamanti K., Ding S., Dinh H. Q., Dirix L., Doddapaneni H. V., Donmez N., Dow M. T., Drapkin R., Drews R. M., Serge S., Dudderidge T., Dueso-Barroso A., Dunford A. J., Dunn M., Duthie F. 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M., Herrmann C., Hersey P., Hilmarsdottir H., Hirano S., Hiraoka N., Hoadley K. A., Hobolth A., Hodzic E., Hoell J. I., Hoffmann S., Hofmann O., Holbrook A., Holik A. Z., Hollingsworth M. A., Holmes O., Holt R. A., Hong C., Hong E. P., Hong J. H., Hooijer G. K., Hornshoj H., Hosoda F., Hou Y., Hovestadt V., Howat W., Hoyle A. P., Hruban R. H., Hu J., Hua X., Huang K. -L., Huang M., Huang M. N., Huber W., Hudson T. J., Hummel M., Hung J. A., Huntsman D., Hupp T. R., Huse J., Huska M. R., Hubschmann D., Iacobuzio-Donahue C. A., Imbusch C. D., Imielinski M., Imoto S., Isaacs W. B., Isaev K., Ishikawa S., Iskar M., Islam S. M. A., Ittmann M., Ivkovic S., Izarzugaza J. M. G., Jacquemier J., Jakrot V., Jamieson N. B., Jang G. H., Jang S. J., Jayaseelan J. C., Jayasinghe R., Jefferys S. R., Jegalian K., Jennings J. L., Jeon S. -H., Jerman L., Ji Y., Jiao W., Johansson P. A., Johns A. L., Johns J., Johnson R., Johnson T. A., Jolly C., Joly Y., Jonasson J. G., Jones C. D., Jones D. T. W., Jones N., Jones S. J. M., Jonkers J., Ju Y. S., Juhl H., Juul M., Juul R. I., Juul S., Kabbe R., Kahles A., Kahraman A., Kaiser V. B., Kakavand H., Kalimuthu S., von Kalle C., Kang K. J., Karaszi K., Karlan B., Karlic R., Karsch D., Kassahn K. S., Katai H., Kato M., Katoh H., Kawakami Y., Kay J. D., Kazakoff S. H., Kazanov M. D., Keays M., Kebebew E., Kefford R. F., Kellis M., Kench J. G., Kennedy C. J., Kerssemakers J. N. A., Khoo D., Khoo V., Khuntikeo N., Khurana E., Kilpinen H., Kim H. K., Kim H. -Y., Kim H., Kim J., Kim J. K., Kim Y., King T. A., Klapper W., Klimczak L. J., Knappskog S., Kneba M., Knoppers B. M., Koh Y., Jan Komorowski, Komura D., Komura M., Kong G., Kool M., Korbel J. O., Korchina V., Korshunov A., Koscher M., Koster R., Kote-Jarai Z., Koures A., Kovacevic M., Kremeyer B., Kretzmer H., Kreuz M., Krishnamurthy S., Kube D., Kumar K., Kumar P., Kundra R., Kubler K., Kuppers R., Lagergren J., Lai P. H., Laird P. W., Lakhani S. R., Lalonde E., Lamaze F. 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C., Vermeulen P., Verrill C., Viari A., Vicente D., Vicentini C., Raghavan K. V., Viksna J., Vilain R. E., Villasante I., Vincent-Salomon A., Visakorpi T., Voet D., Vyas P., Vazquez-Garcia I., Waddell N. M., Waddell N., Wadelius C., Wadi L., Wagener R., Wang L., Wang Q., Wang Y., Wang Z., Waring P. M., Warnatz H. -J., Warrell J., Warren A. Y., Wedge D. C., Weichenhan D., Weinberger P., Weisenberger D. J., Welch I., Whalley J. P., Whitaker H. C., Wigle D., Wilkerson M. D., Williams A., Wilmott J. S., Wilson G. W., Wilson J. M., Wilson R. K., Winterhoff B., Wintersinger J. A., Wiznerowicz M., Wolf S., Wong B. H., Wong T., Wong W., Woo Y., Wood S., Wouters B. G., Wright A. J., Wright D. W., Wright M. H., Wu C. -L., Wu D. -Y., Wu G., Wu J., Wu K., Wu Y., Xia T., Xiang Q., Xiao X., Xing R., Xiong H., Xu Q., Xu Y., Yachida S., Yamaguchi R., Yamamoto M., Yamamoto S., Yamaue H., Yang F., Yang H., Yang J. 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J., van't Veer L., von Mering C., Bailey, M, Meyerson, W, Dursi, L, Wang, L, Dong, G, Liang, W, Weerasinghe, A, Li, S, Li, Y, Kelso, S, Akbani, R, Anur, P, Buchanan, A, Chiotti, K, Covington, K, Creason, A, Ding, L, Ellrott, K, Fan, Y, Foltz, S, Getz, G, Hale, W, Haussler, D, Hess, J, Hutter, C, Kandoth, C, Kasaian, K, Kasapi, M, Larson, D, Leshchiner, I, Letaw, J, Ma, S, Mclellan, M, Men, Y, Mills, G, Niu, B, Peto, M, Radenbaugh, A, Reynolds, S, Saksena, G, Sofia, H, Stewart, C, Struck, A, Stuart, J, Wang, W, Weinstein, J, Wheeler, D, Wong, C, Xi, L, Ye, K, Bieg, M, Boutros, P, Buchhalter, I, Butler, A, Chen, K, Chong, Z, Drechsel, O, Jonathan Dursi, L, Eils, R, Espiritu, S, Fulton, R, Gao, S, Gelpi, J, Gerstein, M, Gonzalez, S, Gut, I, Hach, F, Heinold, M, Hinton, J, Hu, T, Huang, V, Huang, Y, Hutter, B, Jones, D, Jung, J, Jager, N, Kim, H, Kleinheinz, K, Kumar, S, Kumar, Y, Lalansingh, C, Letunic, I, Livitz, D, Ma, E, Maruvka, Y, Mashl, R, Menzies, A, Milovanovic, A, Nielsen, M, 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Science ,MEDLINE ,Medizin ,General Physics and Astronomy ,Pain ,610 Medicine & health ,1600 General Chemistry ,Computational biology ,Biology ,10 kHz spinal cord stimulation ,Genome ,responders ,MC3 Working Group ,General Biochemistry, Genetics and Molecular Biology ,whole exome sequencing ,Machine Learning ,1300 General Biochemistry, Genetics and Molecular Biology ,PCAWG novel somatic mutation calling methods working group ,medicine ,cancer ,Genome mutation ,Exome ,Exome sequencing ,Whole genome sequencing ,whole genome sequencing ,Multidisciplinary ,Published Erratum ,Cancer ,PCAWG Consortium ,General Chemistry ,medicine.disease ,3100 General Physics and Astronomy ,oncology ,10032 Clinic for Oncology and Hematology ,Prediction - Abstract
Weitere Nicht-UDE-Autoren sind nicht genannt. Originalpublikation: 10.1038/s41467-020-18151-y. CA extern The original version of this Article omitted from the author list the 9th author Yize Li, who is from the ‘The McDonnell Genome Institute at Washington University, St. Louis, MO 63108, USA and Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63108, USA’. This has been corrected in both the PDF and HTML versions of the Article. © 2020, The Author(s).
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- 2020
3. Sex differences in oncogenic mutational processes
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Li C. H., Prokopec S. D., Sun R. X., Yousif F., Schmitz N., Al-Shahrour F., Atwal G., Bailey P. J., Biankin A. V., Boutros P. C., Campbell P. J., Chang D. K., Cooke S. L., Deshpande V., Faltas B. M., Faquin W. C., Garraway L., Getz G., Grimmond S. M., Haider S., Hoadley K. A., Jiao W., Kaiser V. B., Karlic R., Kato M., Kubler K., Lazar A. J., Louis D. N., Margolin A., Martin S., Nahal-Bose H. K., Nielsen G. P., Nik-Zainal S., Omberg L., P'ng C., Perry M. D., Polak P., Rheinbay E., Rubin M. A., Semple C. A., Sgroi D. C., Shibata T., Siebert R., Smith J., Stein L. D., Stobbe M. D., Thai K., Wright D. W., Wu C. -L., Yuan K., Zhang J., Aaltonen L. A., Abascal F., Abeshouse A., Aburatani H., Adams D. J., Agrawal N., Ahn K. S., Ahn S. -M., Aikata H., Akbani R., Akdemir K. C., Al-Ahmadie H., Al-Sedairy S. T., Alawi M., Albert M., Aldape K., Alexandrov L. B., Ally A., Alsop K., Alvarez E. G., Amary F., Amin S. B., Aminou B., Ammerpohl O., Anderson M. J., Ang Y., Antonello D., Anur P., Aparicio S., Appelbaum E. L., Arai Y., Aretz A., Arihiro K., Ariizumi S. -I., Armenia J., Arnould L., Asa S., Assenov Y., Aukema S., Auman J. T., Aure M. R., Awadalla P., Aymerich M., Bader G. D., Baez-Ortega A., Bailey M. H., Balasundaram M., Balu S., Bandopadhayay P., Banks R. E., Barbi S., Barbour A. P., Barenboim J., Barnholtz-Sloan J., Barr H., Barrera E., Bartlett J., Bartolome J., Bassi C., Bathe O. F., Baumhoer D., Bavi P., Baylin S. B., Bazant W., Beardsmore D., Beck T. A., Behjati S., Behren A., Niu B., Bell C., Beltran S., Benz C., Berchuck A., Bergmann A. K., Bergstrom E. N., Berman B. P., Berney D. M., Bernhart S. H., Beroukhim R., Berrios M., Bersani S., Bertl J., Betancourt M., Bhandari V., Bhosle S. G., Bieg M., Bigner D., Binder H., Birney E., Birrer M., Biswas N. K., Bjerkehagen B., Bodenheimer T., Boice L., Bonizzato G., De Bono J. S., Boot A., Bootwalla M. S., Borg A., Borkhardt A., Boroevich K. A., Borozan I., Borst C., Bosenberg M., Bosio M., Boultwood J., Bourque G., Bova G. S., Bowen D. T., Bowlby R., Bowtell D. D. L., Boyault S., Boyce R., Boyd J., Brazma A., Brennan P., Brewer D. S., Brinkman A. B., Bristow R. G., Broaddus R. R., Brock J. E., Brock M., Broeks A., Brooks A. N., Brooks D., Brors B., Brunak S., Bruxner T. J. C., Bruzos A. L., Buchanan A., Buchhalter I., Buchholz C., Bullman S., Burke H., Burkhardt B., Burns K. H., Busanovich J., Bustamante C. D., Butler A. P., Butte A. J., Byrne N. J., Borresen-Dale A. -L., Caesar-Johnson S. J., Cafferkey A., Cahill D., Calabrese C., Caldas C., Calvo F., Camacho N., Campo E., Cantu C., Cao S., Carey T. E., Carlevaro-Fita J., Carlsen R., Cataldo I., Cazzola M., Cebon J., Cerfolio R., Chadwick D. E., Chakravarty D., Chalmers D., Chan C. W. Y., Chan K., Chan-Seng-Yue M., Chandan V. S., Chanock S. J., Chantrill L. A., Chateigner A., Chatterjee N., Chayama K., Chen H. -W., Chen J., Chen K., Chen Y., Chen Z., Cherniack A. D., Chien J., Chiew Y. -E., Chin S. -F., Cho J., Cho S., Choi J. K., Choi W., Chomienne C., Chong Z., Choo S. P., Chou A., Christ A. N., Christie E. L., Chuah E., Cibulskis C., Cibulskis K., Cingarlini S., Clapham P., Claviez A., Cleary S., Cloonan N., Cmero M., Collins C. C., Connor A. A., Cooper C. S., Cope L., Corbo V., Cordes M. G., Cordner S. M., Cortes-Ciriano I., Covington K., Cowin P. A., Craft B., Craft D., Creighton C. J., Cun Y., Curley E., Cutcutache I., Czajka K., Czerniak B., Dagg R. A., Danilova L., Davi M. V., Davidson N. R., Davies H., Davis I. J., Davis-Dusenbery B. N., Dawson K. J., De La Vega F. M., De Paoli-Iseppi R., Defreitas T., Dei Tos A. P., Delaneau O., Demchok J. A., Demeulemeester J., Demidov G. M., Demircioglu D., Dennis N. M., Denroche R. E., Dentro S. C., Desai N., Deshwar A. G., Desmedt C., Deu-Pons J., Dhalla N., Dhani N. C., Dhingra P., Dhir R., DiBiase A., Diamanti K., Ding L., Ding S., Dinh H. Q., Dirix L., Doddapaneni H. V., Donmez N., Dow M. T., Drapkin R., Drechsel O., Drews R. M., Serge S., Dudderidge T., Dueso-Barroso A., Dunford A. J., Dunn M., Dursi L. J., Duthie F. R., Dutton-Regester K., Eagles J., Easton D. F., Edmonds S., Edwards P. A., Edwards S. E., Eeles R. A., Ehinger A., Eils J., Eils R., El-Naggar A., Eldridge M., Ellrott K., Erkek S., Escaramis G., Espiritu S. M. G., Estivill X., Etemadmoghadam D., Eyfjord J. E., Fan D., Fan Y., Farcas C., Fassan M., Fatima A., Favero F., Fayzullaev N., Felau I., Fereday S., Ferguson M. L., Ferretti V., Feuerbach L., Field M. A., Fink J. L., Finocchiaro G., Fisher C., Fittall M. W., Fitzgerald A., Fitzgerald R. C., Flanagan A. M., Fleshner N. E., Flicek P., Foekens J. A., Fong K. M., Fonseca N. A., Foster C. S., Fox N. S., Fraser M., Frazer S., Frenkel-Morgenstern M., Friedman W., Frigola J., Fronick C. C., Fujimoto A., Fujita M., Fukayama M., Fulton L. A., Fulton R. S., Furuta M., Futreal P. A., Fullgrabe A., Gabriel S. B., Gallinger S., Gambacorti Passerini C., Gao J., Gao S., Garred O., Garrison E., Garsed D. W., Gehlenborg N., Gelpi J. L. L., George J., Gerhard D. S., Gerhauser C., Gershenwald J. E., Gerstein M., Gerstung M., Ghori M., Ghossein R., Giama N. H., Gibbs R. A., Gill A. J., Gill P., Giri D. D., Glodzik D., Gnanapragasam V. J., Goebler M. E., Goldman M. J., Gomez C., Gonzalez S., Gonzalez-Perez A., Gordenin D. A., Gossage J., Gotoh K., Govindan R., Grabau D., Graham J. S., Grant R. C., Green A. R., Green E., Greger L., Grehan N., Grimaldi S., Grossman R. L., Grundhoff A., Gundem G., Guo Q., Gupta M., Gupta S., Gut I. G., Gut M., Goke J., Ha G., Haake A., Haan D., Haas S., Haase K., Haber J. E., Habermann N., Hach F., Hama N., Hamdy F. C., Hamilton A., Hamilton M. P., Han L., Hanna G. B., Hansmann M., Haradhvala N. J., Harismendy O., Harliwong I., Harmanci A. O., Harrington E., Hasegawa T., Haussler D., Hawkins S., Hayami S., Hayashi S., Hayes D. N., Hayes S. J., Hayward N. K., Hazell S., He Y., Heath A. P., Heath S. C., Hedley D., Hegde A. M., Heiman D. I., Heinold M. C., Heins Z., Heisler L. E., Hellstrom-Lindberg E., Helmy M., Heo S. G., Hepperla A. J., Heredia-Genestar J. M., Herrmann C., Hersey P., Hess J. M., Hilmarsdottir H., Hinton J., Hirano S., Hiraoka N., Hobolth A., Hodzic E., Hoell J. I., Hoffmann S., Hofmann O., Holbrook A., Holik A. Z., Hollingsworth M. A., Holmes O., Holt R. A., Hong C., Hong E. P., Hong J. H., Hooijer G. K., Hornshoj H., Hosoda F., Hou Y., Hovestadt V., Howat W., Hoyle A. P., Hruban R. H., Hu J., Hu T., Hua X., Huang K. -L., Huang M., Huang M. N., Huang V., Huang Y., Huber W., Hudson T. J., Hummel M., Hung J. A., Huntsman D., Hupp T. R., Huse J., Huska M. R., Hutter B., Hutter C. M., Hubschmann D., Iacobuzio-Donahue C. A., Imbusch C. D., Imielinski M., Imoto S., Isaacs W. B., Isaev K., Ishikawa S., Iskar M., Islam S. M. A., Ittmann M., Ivkovic S., Izarzugaza J. M. G., Jacquemier J., Jakrot V., Jamieson N. B., Jang G. H., Jang S. J., Jayaseelan J. C., Jayasinghe R., Jefferys S. R., Jegalian K., Jennings J. L., Jeon S. -H., Jerman L., Ji Y., Johansson P. A., Johns A. L., Johns J., Johnson R., Johnson T. A., Jolly C., Joly Y., Jonasson J. G., Jones C. D., Jones D. R., Jones D. T. W., Jones N., Jones S. J. M., Jonkers J., Ju Y. S., Juhl H., Jung J., Juul M., Juul R. I., Juul S., Jager N., Kabbe R., Kahles A., Kahraman A., Kakavand H., Kalimuthu S., von Kalle C., Kang K. J., Karaszi K., Karlan B., Karsch D., Kasaian K., Kassahn K. S., Katai H., Katoh H., Kawakami Y., Kay J. D., Kazakoff S. H., Kazanov M. D., Keays M., Kebebew E., Kefford R. F., Kellis M., Kench J. G., Kennedy C. J., Kerssemakers J. N. A., Khoo D., Khoo V., Khuntikeo N., Khurana E., Kilpinen H., Kim H. K., Kim H. -L., Kim H. -Y., Kim H., Kim J., Kim J. K., Kim Y., King T. A., Klapper W., Kleinheinz K., Klimczak L. J., Knappskog S., Kneba M., Knoppers B. M., Koh Y., Komorowski J., Komura D., Komura M., Kong G., Kool M., Korbel J. O., Korchina V., Korshunov A., Koscher M., Koster R., Kote-Jarai Z., Koures A., Kovacevic M., Kremeyer B., Kretzmer H., Kreuz M., Krishnamurthy S., Kube D., Kumar K., Kumar P., Kumar S., Kumar Y., Kundra R., Kuppers R., Lagergren J., Lai P. H., Laird P. W., Lakhani S. R., Lalansingh C. M., Lalonde E., Lamaze F. C., Lambert A., Lander E., Landgraf P., Landoni L., Langerod A., Lanzos A., Larsimont D., Larsson E., Lathrop M., Lau L. M. S., Lawerenz C., Lawlor R. T., Lawrence M. S., Le X., Lee D., Lee E. A., Lee H. J., Lee J. J. -K., Lee J. -Y., Lee J., Lee M. T. M., Lee-Six H., Lehmann K. -V., Lehrach H., Lenze D., Leonard C. R., Leongamornlert D. A., Leshchiner I., Letourneau L., Letunic I., Levine D. A., Lewis L., Ley T., Li C., Li H. I., Li J., Li L., Li S., Li X., Li Y., Liang H., Liang S. -B., Lichter P., Lin P., Lin Z., Linehan W. M., Lingjaerde O. C., Liu D., Liu E. M., Liu F. -F., Liu F., Liu J., Liu X., Livingstone J., Livitz D., Livni N., Lochovsky L., Loeffler M., Long G. V., Lopez-Guillermo A., Lou S., Lovat L. B., Lu Y., Lu Y. -J., Luchini C., Lungu I., Luo X., Luxton H. J., Lynch A. G., Lype L., Lopez C., Lopez-Otin C., Ma E. Z., Ma Y., MacGrogan G., MacRae S., Macintyre G., Madsen T., Maejima K., Mafficini A., Maglinte D. T., Maitra A., Majumder P. P., Malcovati L., Malikic S., Malleo G., Mann G. J., Mantovani-Loffler L., Marchal K., Marchegiani G., Mardis E. R., Margolin A. A., Marin M. G., Markowetz F., Markowski J., Marks J., Marques-Bonet T., Marra M. A., Marsden L., Martens J. W. M., Martin-Subero J. I., Martincorena I., Martinez-Fundichely A., Maruvka Y. E., Mashl R. J., Massie C. E., Matthew T. J., Matthews L., Mayer E., Mayes S., Mayo M., Mbabaali F., McCune K., McDermott U., McGillivray P. D., McLellan M. D., McPherson J. D., McPherson J. R., McPherson T. A., Meier S. R., Meng A., Meng S., Menzies A., Merrett N. D., Merson S., Meyerson M., Meyerson W., Mieczkowski P. A., Mihaiescu G. L., Mijalkovic S., Mijalkovic-Lazic A. M., Mikkelsen T., Milella M., Mileshkin L., Miller C. A., Miller D. K., Miller J. K., Mills G. B., Milovanovic A., Minner S., Miotto M., Arnau G. M., Mirabello L., Mitchell C., Mitchell T. J., Miyano S., Miyoshi N., Mizuno S., Molnar-Gabor F., Moore M. J., Moore R. A., Morganella S., Morris Q. D., Morrison C., Mose L. E., Moser C. D., Muinos F., Mularoni L., Mungall A. J., Mungall K., Musgrove E. A., Mustonen V., Mutch D., Muyas F., Muzny D. M., Munoz A., Myers J., Myklebost O., Moller P., Nagae G., Nagrial A. M., Nakagama H., Nakagawa H., Nakamura H., Nakamura T., Nakano K., Nandi T., Nangalia J., Nastic M., Navarro A., Navarro F. C. P., Neal D. E., Nettekoven G., Newell F., Newhouse S. J., Newton Y., Ng A. W. T., Ng A., Nicholson J., Nicol D., Nie Y., Nielsen M. M., Noble M. S., Nones K., Northcott P. A., Notta F., O'Connor B. D., O'Donnell P., O'Donovan M., O'Meara S., O'Neill B. P., O'Neill J. R., Ocana D., Ochoa A., Oesper L., Ogden C., Ohdan H., Ohi K., Ohno-Machado L., Oien K. A., Ojesina A. I., Ojima H., Okusaka T., Ong C. K., Ossowski S., Ott G., Ouellette B. F. F., Paczkowska M., Paiella S., Pairojkul C., Pajic M., Pan-Hammarstrom Q., Papaemmanuil E., Papatheodorou I., Paramasivam N., Park J. W., Park J. -W., Park K., Park P. J., Parker J. S., Parsons S. L., Pass H., Pasternack D., Pastore A., Patch A. -M., Pauporte I., Pea A., Pearson J. V., Pedamallu C. S., Pedersen J. S., Pederzoli P., Peifer M., Pennell N. A., Perou C. M., Petersen G. M., Peto M., Petrelli N., Petryszak R., Pfister S. M., Phillips M., Pich O., Pickett H. A., Pihl T. D., Pillay N., Pinder S., Pinese M., Pinho A. V., Pitkanen E., Pivot X., Pineiro-Yanez E., Planko L., Plass C., Pons T., Popescu I., Potapova O., Prasad A., Preston S. R., Prinz M., Pritchard A. L., Provenzano E., Puente X. S., Puig S., Puiggros M., Pulido-Tamayo S., Pupo G. M., Purdie C. A., Quinn M. C., Rabionet R., Rader J. S., Radlwimmer B., Radovic P., Raeder B., Raine K. M., Ramakrishna M., Ramakrishnan K., Ramalingam S., Raphael B. J., Rathmell W. K., Rausch T., Reifenberger G., Reimand J., Reis-Filho J., Reuter V., Reyes-Salazar I., Reyna M. A., Reynolds S. M., Riazalhosseini Y., Richardson A. L., Richter J., Ringel M., Ringner M., Rino Y., Rippe K., Roach J., Roberts L. R., Roberts N. D., Roberts S. A., Robertson A. G., Robertson A. J., Rodriguez J. B., Rodriguez-Martin B., Rodriguez-Gonzalez F. G., Roehrl M. H. A., Rohde M., Rokutan H., Romieu G., Rooman I., Roques T., Rosebrock D., Rosenberg M., Rosenstiel P. C., Rosenwald A., Rowe E. W., Royo R., Rozen S. G., Rubanova Y., Rubio-Perez C., Rudneva V. A., Rusev B. C., Ruzzenente A., Ratsch G., Sabarinathan R., Sabelnykova V. Y., Sadeghi S., Sahinalp S. C., Saini N., Saito-Adachi M., Saksena G., Salcedo A., Salgado R., Salichos L., Sallari R., Saller C., Salvia R., Sam M., Samra J. S., Sanchez-Vega F., Sander C., Sanders G., Sarin R., Sarrafi I., Sasaki-Oku A., Sauer T., Sauter G., Saw R. P. M., Scardoni M., Scarlett C. J., Scarpa A., Scelo G., Schadendorf D., Schein J. E., Schilhabel M. B., Schlesner M., Schlomm T., Schmidt H. K., Schramm S. -J., Schreiber S., Schultz N., Schumacher S. E., Schwarz R. F., Scolyer R. A., Scott D., Scully R., Seethala R., Segre A. V., Selander I., Senbabaoglu Y., Sengupta S., Sereni E., Serra S., Shackleton M., Shah N. C., Shahabi S., Shang C. A., Shang P., Shapira O., Shelton T., Shen C., Shen H., Shepherd R., Shi R., Shi Y., Shiah Y. -J., Shih J., Shimizu E., Shimizu K., Shin S. J., Shiraishi Y., Shmaya T., Shmulevich I., Shorser S. I., Short C., Shrestha R., Shringarpure S. S., Shriver C., Shuai S., Sidiropoulos N., Sieuwerts A. M., Sieverling L., Signoretti S., Sikora K. O., Simbolo M., Simon R., Simons J. V., Simpson J. T., Simpson P. T., Singer S., Sinnott-Armstrong N., Sipahimalani P., Skelly T. J., Smid M., Smith-McCune K., Socci N. D., Sofia H. J., Soloway M. G., Song L., Sood A. K., Sothi S., Sotiriou C., Soulette C. M., Span P. N., Spellman P. T., Sperandio N., Spillane A. J., Spiro O., Spring J., Staaf J., Stadler P. F., Staib P., Stark S. G., Stebbings L., Stefansson O. A., Stegle O., Stenhouse A., Stewart C., Stilgenbauer S., Stratton M. R., Stretch J. R., Struck A. J., Stuart J. M., Stunnenberg H. G., Su H., Su X., Sungalee S., Susak H., Suzuki A., Sweep F., Szczepanowski M., Sultmann H., Yugawa T., Tam A., Tamborero D., Tan B. K. T., Tan D., Tan P., Tanaka H., Taniguchi H., Tanskanen T. J., Tarabichi M., Tarnuzzer R., Tarpey P., Taschuk M. L., Tatsuno K., Tavare S., Taylor D. F., Taylor-Weiner A., Teague J. W., Teh B. T., Tembe V., Temes J., Thayer S. P., Thiessen N., Thomas G., Thomas S., Thompson A., Thompson A. M., Thompson J. F., Thompson R. H., Thorne H., Thorne L. B., Thorogood A., Tiao G., Tijanic N., Timms L. E., Tirabosco R., Tojo M., Tommasi S., Toon C. W., Toprak U. H., Torrents D., Tortora G., Tost J., Totoki Y., Townend D., Traficante N., Treilleux I., Trotta J. -R., Trumper L. H. 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D., Williams A., Wilmott J. S., Wilson G. W., Wilson J. M., Wilson R. K., Winterhoff B., Wintersinger J. A., Wiznerowicz M., Wolf S., Wong B. H., Wong T., Wong W., Woo Y., Wood S., Wouters B. G., Wright A. J., Wright M. H., Wu D. -Y., Wu G., Wu J., Wu K., Wu Y., Wu Z., Xi L., Xia T., Xiang Q., Xiao X., Xing R., Xiong H., Xu Q., Xu Y., Xue H., Yachida S., Yakneen S., Yamaguchi R., Yamaguchi T. N., Yamamoto M., Yamamoto S., Yamaue H., Yang F., Yang H., Yang J. Y., Yang L., Yang S., Yang T. -P., Yang Y., Yao X., Yaspo M. -L., Yates L., Yau C., Ye C., Ye K., Yellapantula V. D., Yoon C. J., Yoon S. -S., Yu J., Yu K., Yu W., Yu Y., Yuan Y., Yuen D., Yung C. K., Zaikova O., Zamora J., Zapatka M., Zenklusen J. C., Zenz T., Zeps N., Zhang C. -Z., Zhang F., Zhang H., Zhang X., Zhang Y., Zhang Z., Zhao Z., Zheng L., Zheng X., Zhou W., Zhou Y., Zhu B., Zhu H., Zhu J., Zhu S., Zou L., Zou X., deFazio A., van As N., van Deurzen C. H. M., van de Vijver M. J., Veer L., von Mering C., Lauri Antti Aaltonen / Principal Investigator, Genome-Scale Biology (GSB) Research Program, Department of Medical and Clinical Genetics, Organismal and Evolutionary Biology Research Programme, Helsinki Institute for Information Technology, Institute of Biotechnology, Bioinformatics, Department of Computer Science, Faculty of Medicine, HUS Helsinki and Uusimaa Hospital District, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, University of St Andrews. Statistics, University of St Andrews. School of Medicine, Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Li, C, Prokopec, S, Sun, R, Yousif, F, Schmitz, N, Al-Shahrour, F, Atwal, G, Bailey, P, Biankin, A, Boutros, P, Campbell, P, Chang, D, Cooke, S, Deshpande, V, Faltas, B, Faquin, W, Garraway, L, Getz, G, Grimmond, S, Haider, S, Hoadley, K, Jiao, W, Kaiser, V, Karlic, R, Kato, M, Kubler, K, Lazar, A, Louis, D, Margolin, A, Martin, S, Nahal-Bose, H, Nielsen, G, Nik-Zainal, S, Omberg, L, P'Ng, C, Perry, M, Polak, P, Rheinbay, E, Rubin, M, Semple, C, Sgroi, D, Shibata, T, Siebert, R, Smith, J, Stein, L, Stobbe, M, Thai, K, Wright, D, Wu, C, Yuan, K, Zhang, J, Aaltonen, L, Abascal, F, Abeshouse, A, Aburatani, H, Adams, D, Agrawal, N, Ahn, K, Ahn, S, Aikata, H, Akbani, R, Akdemir, K, Al-Ahmadie, H, Al-Sedairy, S, Alawi, M, Albert, M, Aldape, K, Alexandrov, L, Ally, A, Alsop, K, Alvarez, E, Amary, F, Amin, S, Aminou, B, Ammerpohl, O, Anderson, M, Ang, Y, Antonello, D, Anur, P, Aparicio, S, Appelbaum, E, Arai, Y, Aretz, A, Arihiro, K, Ariizumi, S, Armenia, J, Arnould, L, Asa, S, Assenov, Y, Aukema, S, Auman, J, Aure, M, Awadalla, P, Aymerich, M, Bader, G, Baez-Ortega, A, Bailey, M, Balasundaram, M, Balu, S, Bandopadhayay, P, Banks, R, Barbi, S, Barbour, A, Barenboim, J, Barnholtz-Sloan, J, Barr, H, Barrera, E, Bartlett, J, Bartolome, J, Bassi, C, Bathe, O, Baumhoer, D, Bavi, P, Baylin, S, Bazant, W, Beardsmore, D, Beck, T, Behjati, S, Behren, A, Niu, B, Bell, C, Beltran, S, Benz, C, Berchuck, A, Bergmann, A, Bergstrom, E, Berman, B, Berney, D, Bernhart, S, Beroukhim, R, Berrios, M, Bersani, S, Bertl, J, Betancourt, M, Bhandari, V, Bhosle, S, Bieg, M, Bigner, D, Binder, H, Birney, E, Birrer, M, Biswas, N, Bjerkehagen, B, Bodenheimer, T, Boice, L, Bonizzato, G, De Bono, J, Boot, A, Bootwalla, M, Borg, A, Borkhardt, A, Boroevich, K, Borozan, I, Borst, C, Bosenberg, M, Bosio, M, Boultwood, J, Bourque, G, Bova, G, Bowen, D, Bowlby, R, Bowtell, D, Boyault, S, Boyce, R, Boyd, J, Brazma, A, Brennan, P, Brewer, D, Brinkman, A, Bristow, R, Broaddus, R, Brock, J, Brock, M, Broeks, A, Brooks, A, Brooks, D, Brors, B, Brunak, S, Bruxner, T, Bruzos, A, Buchanan, A, Buchhalter, I, Buchholz, C, Bullman, S, Burke, H, Burkhardt, B, Burns, K, Busanovich, J, Bustamante, C, Butler, A, Butte, A, Byrne, N, Borresen-Dale, A, Caesar-Johnson, S, Cafferkey, A, Cahill, D, Calabrese, C, Caldas, C, Calvo, F, Camacho, N, Campo, E, Cantu, C, Cao, S, Carey, T, Carlevaro-Fita, J, Carlsen, R, Cataldo, I, Cazzola, M, Cebon, J, Cerfolio, R, Chadwick, D, Chakravarty, D, Chalmers, D, Chan, C, Chan, K, Chan-Seng-Yue, M, Chandan, V, Chanock, S, Chantrill, L, Chateigner, A, Chatterjee, N, Chayama, K, Chen, H, Chen, J, Chen, K, Chen, Y, Chen, Z, Cherniack, A, Chien, J, Chiew, Y, Chin, S, Cho, J, Cho, S, Choi, J, Choi, W, Chomienne, C, Chong, Z, Choo, S, Chou, A, Christ, A, Christie, E, Chuah, E, Cibulskis, C, Cibulskis, K, Cingarlini, S, Clapham, P, Claviez, A, Cleary, S, Cloonan, N, Cmero, M, Collins, C, Connor, A, Cooper, C, Cope, L, Corbo, V, Cordes, M, Cordner, S, Cortes-Ciriano, I, Covington, K, Cowin, P, Craft, B, Craft, D, Creighton, C, Cun, Y, Curley, E, Cutcutache, I, Czajka, K, Czerniak, B, Dagg, R, Danilova, L, Davi, M, Davidson, N, Davies, H, Davis, I, Davis-Dusenbery, B, Dawson, K, De La Vega, F, De Paoli-Iseppi, R, Defreitas, T, Dei Tos, A, Delaneau, O, Demchok, J, Demeulemeester, J, Demidov, G, Demircioglu, D, Dennis, N, Denroche, R, Dentro, S, Desai, N, Deshwar, A, Desmedt, C, Deu-Pons, J, Dhalla, N, Dhani, N, Dhingra, P, Dhir, R, Dibiase, A, Diamanti, K, Ding, L, Ding, S, Dinh, H, Dirix, L, Doddapaneni, H, Donmez, N, Dow, M, Drapkin, R, Drechsel, O, Drews, R, Serge, S, Dudderidge, T, Dueso-Barroso, A, Dunford, A, Dunn, M, Dursi, L, Duthie, F, Dutton-Regester, K, Eagles, J, Easton, D, Edmonds, S, Edwards, P, Edwards, S, Eeles, R, Ehinger, A, Eils, J, Eils, R, El-Naggar, A, Eldridge, M, Ellrott, K, Erkek, S, Escaramis, G, Espiritu, S, Estivill, X, Etemadmoghadam, D, Eyfjord, J, Fan, D, Fan, Y, Farcas, C, Fassan, M, Fatima, A, Favero, F, Fayzullaev, N, Felau, I, Fereday, S, Ferguson, M, Ferretti, V, Feuerbach, L, Field, M, Fink, J, Finocchiaro, G, Fisher, C, Fittall, M, Fitzgerald, A, Fitzgerald, R, Flanagan, A, Fleshner, N, Flicek, P, Foekens, J, Fong, K, Fonseca, N, Foster, C, Fox, N, Fraser, M, Frazer, S, Frenkel-Morgenstern, M, Friedman, W, Frigola, J, Fronick, C, Fujimoto, A, Fujita, M, Fukayama, M, Fulton, L, Fulton, R, Furuta, M, Futreal, P, Fullgrabe, A, Gabriel, S, Gallinger, S, Gambacorti Passerini, C, Gao, J, Gao, S, Garred, O, Garrison, E, Garsed, D, Gehlenborg, N, Gelpi, J, George, J, Gerhard, D, Gerhauser, C, Gershenwald, J, Gerstein, M, Gerstung, M, Ghori, M, Ghossein, R, Giama, N, Gibbs, R, Gill, A, Gill, P, Giri, D, Glodzik, D, Gnanapragasam, V, Goebler, M, Goldman, M, Gomez, C, Gonzalez, S, Gonzalez-Perez, A, Gordenin, D, Gossage, J, Gotoh, K, Govindan, R, Grabau, D, Graham, J, Grant, R, Green, A, Green, E, Greger, L, Grehan, N, Grimaldi, S, Grossman, R, Grundhoff, A, Gundem, G, Guo, Q, Gupta, M, Gupta, S, Gut, I, Gut, M, Goke, J, Ha, G, Haake, A, Haan, D, Haas, S, Haase, K, Haber, J, Habermann, N, Hach, F, Hama, N, Hamdy, F, Hamilton, A, Hamilton, M, Han, L, Hanna, G, Hansmann, M, Haradhvala, N, Harismendy, O, Harliwong, I, Harmanci, A, Harrington, E, Hasegawa, T, Haussler, D, Hawkins, S, Hayami, S, Hayashi, S, Hayes, D, Hayes, S, Hayward, N, Hazell, S, He, Y, Heath, A, Heath, S, Hedley, D, Hegde, A, Heiman, D, Heinold, M, Heins, Z, Heisler, L, Hellstrom-Lindberg, E, Helmy, M, Heo, S, Hepperla, A, Heredia-Genestar, J, Herrmann, C, Hersey, P, Hess, J, Hilmarsdottir, H, Hinton, J, Hirano, S, Hiraoka, N, Hobolth, A, Hodzic, E, Hoell, J, Hoffmann, S, Hofmann, O, Holbrook, A, Holik, A, Hollingsworth, M, Holmes, O, Holt, R, Hong, C, Hong, E, Hong, J, Hooijer, G, Hornshoj, H, Hosoda, F, Hou, Y, Hovestadt, V, Howat, W, Hoyle, A, Hruban, R, Hu, J, Hu, T, Hua, X, Huang, K, Huang, M, Huang, V, Huang, Y, Huber, W, Hudson, T, Hummel, M, Hung, J, Huntsman, D, Hupp, T, Huse, J, Huska, M, Hutter, B, Hutter, C, Hubschmann, D, Iacobuzio-Donahue, C, Imbusch, C, Imielinski, M, Imoto, S, Isaacs, W, Isaev, K, Ishikawa, S, Iskar, M, Islam, S, Ittmann, M, Ivkovic, S, Izarzugaza, J, Jacquemier, J, Jakrot, V, Jamieson, N, Jang, G, Jang, S, Jayaseelan, J, Jayasinghe, R, Jefferys, S, Jegalian, K, Jennings, J, Jeon, S, Jerman, L, Ji, Y, Johansson, P, Johns, A, Johns, J, Johnson, R, Johnson, T, Jolly, C, Joly, Y, Jonasson, J, Jones, C, Jones, D, Jones, N, Jones, S, Jonkers, J, Ju, Y, Juhl, H, Jung, J, Juul, M, Juul, R, Juul, S, Jager, N, Kabbe, R, Kahles, A, Kahraman, A, Kakavand, H, Kalimuthu, S, von Kalle, C, Kang, K, Karaszi, K, Karlan, B, Karsch, D, Kasaian, K, Kassahn, K, Katai, H, Katoh, H, Kawakami, Y, Kay, J, Kazakoff, S, Kazanov, M, Keays, M, Kebebew, E, Kefford, R, Kellis, M, Kench, J, Kennedy, C, Kerssemakers, J, Khoo, D, Khoo, V, Khuntikeo, N, Khurana, E, Kilpinen, H, Kim, H, Kim, J, Kim, Y, King, T, Klapper, W, Kleinheinz, K, Klimczak, L, Knappskog, S, Kneba, M, Knoppers, B, Koh, Y, Komorowski, J, Komura, D, Komura, M, Kong, G, Kool, M, Korbel, J, Korchina, V, Korshunov, A, Koscher, M, Koster, R, Kote-Jarai, Z, Koures, A, Kovacevic, M, Kremeyer, B, Kretzmer, H, Kreuz, M, Krishnamurthy, S, Kube, D, Kumar, K, Kumar, P, Kumar, S, Kumar, Y, Kundra, R, Kuppers, R, Lagergren, J, Lai, P, Laird, P, Lakhani, S, Lalansingh, C, Lalonde, E, Lamaze, F, Lambert, A, Lander, E, Landgraf, P, Landoni, L, Langerod, A, Lanzos, A, Larsimont, D, Larsson, E, Lathrop, M, Lau, L, Lawerenz, C, Lawlor, R, Lawrence, M, Le, X, Lee, D, Lee, E, Lee, H, Lee, J, Lee, M, Lee-Six, H, Lehmann, K, Lehrach, H, Lenze, D, Leonard, C, Leongamornlert, D, Leshchiner, I, Letourneau, L, Letunic, I, Levine, D, Lewis, L, Ley, T, Li, H, Li, J, Li, L, Li, S, Li, X, Li, Y, Liang, H, Liang, S, Lichter, P, Lin, P, Lin, Z, Linehan, W, Lingjaerde, O, Liu, D, Liu, E, Liu, F, Liu, J, Liu, X, Livingstone, J, Livitz, D, Livni, N, Lochovsky, L, Loeffler, M, Long, G, Lopez-Guillermo, A, Lou, S, Lovat, L, Lu, Y, Luchini, C, Lungu, I, Luo, X, Luxton, H, Lynch, A, Lype, L, Lopez, C, Lopez-Otin, C, Ma, E, Ma, Y, Macgrogan, G, Macrae, S, Macintyre, G, Madsen, T, Maejima, K, Mafficini, A, Maglinte, D, Maitra, A, Majumder, P, Malcovati, L, Malikic, S, Malleo, G, Mann, G, Mantovani-Loffler, L, Marchal, K, Marchegiani, G, Mardis, E, Marin, M, Markowetz, F, Markowski, J, Marks, J, Marques-Bonet, T, Marra, M, Marsden, L, Martens, J, Martin-Subero, J, Martincorena, I, Martinez-Fundichely, A, Maruvka, Y, Mashl, R, Massie, C, Matthew, T, Matthews, L, Mayer, E, Mayes, S, Mayo, M, Mbabaali, F, Mccune, K, Mcdermott, U, Mcgillivray, P, Mclellan, M, Mcpherson, J, Mcpherson, T, Meier, S, Meng, A, Meng, S, Menzies, A, Merrett, N, Merson, S, Meyerson, M, Meyerson, W, Mieczkowski, P, Mihaiescu, G, Mijalkovic, S, Mijalkovic-Lazic, A, Mikkelsen, T, Milella, M, Mileshkin, L, Miller, C, Miller, D, Miller, J, Mills, G, Milovanovic, A, Minner, S, Miotto, M, Arnau, G, Mirabello, L, Mitchell, C, Mitchell, T, Miyano, S, Miyoshi, N, Mizuno, S, Molnar-Gabor, F, Moore, M, Moore, R, Morganella, S, Morris, Q, Morrison, C, Mose, L, Moser, C, Muinos, F, Mularoni, L, Mungall, A, Mungall, K, Musgrove, E, Mustonen, V, Mutch, D, Muyas, F, Muzny, D, Munoz, A, Myers, J, Myklebost, O, Moller, P, Nagae, G, Nagrial, A, Nakagama, H, Nakagawa, H, Nakamura, H, Nakamura, T, Nakano, K, Nandi, T, Nangalia, J, Nastic, M, Navarro, A, Navarro, F, Neal, D, Nettekoven, G, Newell, F, Newhouse, S, Newton, Y, Ng, A, Nicholson, J, Nicol, D, Nie, Y, Nielsen, M, Noble, M, Nones, K, Northcott, P, Notta, F, O'Connor, B, O'Donnell, P, O'Donovan, M, O'Meara, S, O'Neill, B, O'Neill, J, Ocana, D, Ochoa, A, Oesper, L, Ogden, C, Ohdan, H, Ohi, K, Ohno-Machado, L, Oien, K, Ojesina, A, Ojima, H, Okusaka, T, Ong, C, Ossowski, S, Ott, G, Ouellette, B, Paczkowska, M, Paiella, S, Pairojkul, C, Pajic, M, Pan-Hammarstrom, Q, Papaemmanuil, E, Papatheodorou, I, Paramasivam, N, Park, J, Park, K, Park, P, Parker, J, Parsons, S, Pass, H, Pasternack, D, Pastore, A, Patch, A, Pauporte, I, Pea, A, Pearson, J, Pedamallu, C, Pedersen, J, Pederzoli, P, Peifer, M, Pennell, N, Perou, C, Petersen, G, Peto, M, Petrelli, N, Petryszak, R, Pfister, S, Phillips, M, Pich, O, Pickett, H, Pihl, T, Pillay, N, Pinder, S, Pinese, M, Pinho, A, Pitkanen, E, Pivot, X, Pineiro-Yanez, E, Planko, L, Plass, C, Pons, T, Popescu, I, Potapova, O, Prasad, A, Preston, S, Prinz, M, Pritchard, A, Provenzano, E, Puente, X, Puig, S, Puiggros, M, Pulido-Tamayo, S, Pupo, G, Purdie, C, Quinn, M, Rabionet, R, Rader, J, Radlwimmer, B, Radovic, P, Raeder, B, Raine, K, Ramakrishna, M, Ramakrishnan, K, Ramalingam, S, Raphael, B, Rathmell, W, Rausch, T, Reifenberger, G, Reimand, J, Reis-Filho, J, Reuter, V, Reyes-Salazar, I, Reyna, M, Reynolds, S, Riazalhosseini, Y, Richardson, A, Richter, J, Ringel, M, Ringner, M, Rino, Y, Rippe, K, Roach, J, Roberts, L, Roberts, N, Roberts, S, Robertson, A, Rodriguez, J, Rodriguez-Martin, B, Rodriguez-Gonzalez, F, Roehrl, M, Rohde, M, Rokutan, H, Romieu, G, Rooman, I, Roques, T, Rosebrock, D, Rosenberg, M, Rosenstiel, P, Rosenwald, A, Rowe, E, Royo, R, Rozen, S, Rubanova, Y, Rubio-Perez, C, Rudneva, V, Rusev, B, Ruzzenente, A, Ratsch, G, Sabarinathan, R, Sabelnykova, V, Sadeghi, S, Sahinalp, S, Saini, N, Saito-Adachi, M, Saksena, G, Salcedo, A, Salgado, R, Salichos, L, Sallari, R, Saller, C, Salvia, R, Sam, M, Samra, J, Sanchez-Vega, F, Sander, C, Sanders, G, Sarin, R, Sarrafi, I, Sasaki-Oku, A, Sauer, T, Sauter, G, Saw, R, Scardoni, M, Scarlett, C, Scarpa, A, Scelo, G, Schadendorf, D, Schein, J, Schilhabel, M, Schlesner, M, Schlomm, T, Schmidt, H, Schramm, S, Schreiber, S, Schultz, N, Schumacher, S, Schwarz, R, Scolyer, R, Scott, D, Scully, R, Seethala, R, Segre, A, Selander, I, Senbabaoglu, Y, Sengupta, S, Sereni, E, Serra, S, Shackleton, M, Shah, N, Shahabi, S, Shang, C, Shang, P, Shapira, O, Shelton, T, Shen, C, Shen, H, Shepherd, R, Shi, R, Shi, Y, Shiah, Y, Shih, J, Shimizu, E, Shimizu, K, Shin, S, Shiraishi, Y, Shmaya, T, Shmulevich, I, Shorser, S, Short, C, Shrestha, R, Shringarpure, S, Shriver, C, Shuai, S, Sidiropoulos, N, Sieuwerts, A, Sieverling, L, Signoretti, S, Sikora, K, Simbolo, M, Simon, R, Simons, J, Simpson, J, Simpson, P, Singer, S, Sinnott-Armstrong, N, Sipahimalani, P, Skelly, T, Smid, M, Smith-McCune, K, Socci, N, Sofia, H, Soloway, M, Song, L, Sood, A, Sothi, S, Sotiriou, C, Soulette, C, Span, P, Spellman, P, Sperandio, N, Spillane, A, Spiro, O, Spring, J, Staaf, J, Stadler, P, Staib, P, Stark, S, Stebbings, L, Stefansson, O, Stegle, O, Stenhouse, A, Stewart, C, Stilgenbauer, S, Stratton, M, Stretch, J, Struck, A, Stuart, J, Stunnenberg, H, Su, H, Su, X, Sungalee, S, Susak, H, Suzuki, A, Sweep, F, Szczepanowski, M, Sultmann, H, Yugawa, T, Tam, A, Tamborero, D, Tan, B, Tan, D, Tan, P, Tanaka, H, Taniguchi, H, Tanskanen, T, Tarabichi, M, Tarnuzzer, R, Tarpey, P, Taschuk, M, Tatsuno, K, Tavare, S, Taylor, D, Taylor-Weiner, A, Teague, J, Teh, B, Tembe, V, Temes, J, Thayer, S, Thiessen, N, Thomas, G, Thomas, S, Thompson, A, Thompson, J, Thompson, R, Thorne, H, Thorne, L, Thorogood, A, Tiao, G, Tijanic, N, Timms, L, Tirabosco, R, Tojo, M, Tommasi, S, Toon, C, Toprak, U, Torrents, D, Tortora, G, Tost, J, Totoki, Y, Townend, D, Traficante, N, Treilleux, I, Trotta, J, Trumper, L, Tsao, M, Tsunoda, T, Tubio, J, Tucker, O, Turkington, R, Turner, D, Tutt, A, Ueno, M, Ueno, N, Umbricht, C, Umer, H, Underwood, T, Urban, L, Urushidate, T, Ushiku, T, Uuskula-Reimand, L, Valencia, A, Van Den Berg, D, Van Laere, S, Van Loo, P, Van Meir, E, Van den Eynden, G, Van der Kwast, T, Vasudev, N, Vazquez, M, Vedururu, R, Veluvolu, U, Vembu, S, Verbeke, L, Vermeulen, P, Verrill, C, Viari, A, Vicente, D, Vicentini, C, Raghavan, K, Viksna, J, Vilain, R, Villasante, I, Vincent-Salomon, A, Visakorpi, T, Voet, D, Vyas, P, Vazquez-Garcia, I, Waddell, N, Wadelius, 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C, Zhang, F, Zhang, H, Zhang, X, Zhang, Y, Zhang, Z, Zhao, Z, Zheng, L, Zheng, X, Zhou, W, Zhou, Y, Zhu, B, Zhu, H, Zhu, J, Zhu, S, Zou, L, Zou, X, Defazio, A, van As, N, van Deurzen, C, van de Vijver, M, Veer, L, von Mering, C, Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Genome Canada, Canada Foundation for Innovation, National Institutes of Health (US), National Cancer Institute (US), Pathology, CCA - Cancer biology and immunology, Graduate School, Laboratory Genetic Metabolic Diseases, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Li, Constance H. [0000-0002-5487-7225], Prokopec, Stephenie D. [0000-0001-7936-8577], Boutros, Paul C. [0000-0003-0553-7520], Apollo - University of Cambridge Repository, Tampere University, BioMediTech, TAYS Cancer Centre, Basic (bio-) Medical Sciences, Li, Constance H [0000-0002-5487-7225], Prokopec, Stephenie D [0000-0001-7936-8577], Boutros, Paul C [0000-0003-0553-7520], and Medical Oncology
- Subjects
sex differences ,Male ,Colorectal cancer ,Kynferði ,02 engineering and technology ,0302 clinical medicine ,DISPARITIES ,Epidemiology of cancer ,Cancer genomics ,lcsh:Science ,Càncer ,Cancer genetics, Genome informatics, Cancer genomics, Oncogenes ,Cancer genetics ,Exome ,Cancer ,0303 health sciences ,Mutation ,Neoplasms -- genetics ,1184 Genetics, developmental biology, physiology ,Neoplasms/genetics ,3. Good health ,030220 oncology & carcinogenesis ,Medical genetics ,0210 nano-technology ,Human ,Sex characteristics ,medicine.medical_specialty ,Science ,Genomic Instability ,General Biochemistry, Genetics and Molecular Biology ,RC0254 ,Càncer -- Epidemiologia ,Open Reading Frames ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Chromosomal Instability ,Sex differences ,Genetics ,Humans ,beta Catenin -- genetics ,Sex organ ,SIGNATURES ,45 ,RC0254 Neoplasms. Tumors. Oncology (including Cancer) ,Oncogenes ,medicine.disease ,692/4028/67/69 ,Cancérologie ,Genòmica ,Logistic Models ,030104 developmental biology ,lcsh:Q ,PCAWG Tumour Subtypes and Clinical Translation ,Human genome ,119 ,0301 basic medicine ,Medizin ,General Physics and Astronomy ,medicine.disease_cause ,Bioinformatics ,Genome informatics ,Genome ,Neoplasms ,38/23 ,Medicine and Health Sciences ,Body Size ,beta Catenin ,Sex Characteristics ,318 Medical biotechnology ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,Multidisciplinary ,article ,3rd-DAS ,021001 nanoscience & nanotechnology ,humanities ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Causality ,oncology ,1181 Ecology, evolutionary biology ,SURVIVAL ,631/114/2785 ,Female ,Càncer -- Tractament ,Oncogenes -- genetics ,beta Catenin/genetics ,3122 Cancers ,610 Medicine & health ,QH426 Genetics ,Biology ,Cancer epidemiology ,Rare Diseases ,631/67/68 ,Krabbameinsrannsóknir ,medicine ,ddc:610 ,Gene ,QH426 ,030304 developmental biology ,Krabbamein ,Oncogenes/genetics ,Genome, Human ,Sex organs ,Human Genome ,PCAWG Consortium ,General Chemistry ,GENE ,Good Health and Well Being ,Estudis de gènere ,oncogenic mutational processes ,692/4028/67/395 ,Diferències entre sexes ,Gender studies ,3111 Biomedicine - Abstract
Publisher's version (útgefin grein), Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research., We thank all the members of the Boutros lab for insightful discussions. This study was conducted with the support of the Ontario Institute for Cancer Research to P.C.B. through funding provided by the Government of Ontario. This work was supported by the Discovery Frontiers: Advancing Big Data Science in Genomics Research program, which is jointly funded by the Natural Sciences and Engineering Research Council (NSERC) of Canada, the Canadian Institutes of Health Research (CIHR), Genome Canada and the Canada Foundation for Innovation (CFI). P.C.B. was supported by a Terry Fox Research Institute New Investigator Award and a CIHR New Investigator Award. This work was supported by an NSERC Discovery grant and by Canadian Institutes of Health Research, grant #SVB-145586, to P.C.B. This work was supported by the NIH/NCI under award number P30CA016042 and an operating grant from the National Cancer Institute Early Detection Research Network (1U01CA214194-01). We acknowledge the contributions of the many clinical networks across ICGC and TCGA who provided samples and data to the PCAWG Consortium, and the contributions of the Technical Working Group and the Germline Working Group of the PCAWG Consortium for collation, realignment and harmonised variant calling of the cancer genomes used in this study. We thank the patients and their families for their participation in the individual ICGC and TCGA projects.
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- 2020
4. DEK oncoprotein regulates transcriptional modifiers and sustains tumor initiation activity in high-grade neuroendocrine carcinoma of the lung
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Shibata, T, Kokubu, A, Miyamoto, M, Hosoda, F, Gotoh, M, Tsuta, K, Asamura, H, Matsuno, Y, Kondo, T, Imoto, I, Inazawa, J, and Hirohashi, S
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- 2010
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5. Fusion of MOZ and p300 histone acetyltransferases in acute monocytic leukemia with a t(8;22)(p11;q13) chromosome translocation
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Kitabayashi, I, Aikawa, Y, Yokoyama, A, Hosoda, F, Nagai, M, Kakazu, N, Abe, T, and Ohki, M
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- 2001
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6. Integrated genomic and functional analyses reveal glyoxalase I as a novel metabolic oncogene in human gastric cancer
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Hosoda, F, primary, Arai, Y, additional, Okada, N, additional, Shimizu, H, additional, Miyamoto, M, additional, Kitagawa, N, additional, Katai, H, additional, Taniguchi, H, additional, Yanagihara, K, additional, Imoto, I, additional, Inazawa, J, additional, Ohki, M, additional, and Shibata, T, additional
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- 2014
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7. Report of the Sixth International Workshop on Human Chromosome 11 Mapping 1998. Nice, France, May 2-5, 1998
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Gaudray, P., Carle, G. F., Gerhard, D. S., Gessler, M., Mannens, M. M., Athanasiou, M., Bliek, J., Calender, A., Debelenko, L. V., Devignes, M., Evans, G. A., Favier, R., Forbes, S., Gaudray, G., Gawin, B., Gordon, M., Grimmond, S., Grossfeld, P., Harris, J., Hattori, M., Hosoda, F., Hummerich, H., James, M., Kalla, J., Katsanis, N., and Other departments
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- 1999
8. 904 Copy number alterations in urothelial carcinomas: Their clinicopathological significance and correlation with DNA methylation alterations
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Nishiyama, N., primary, Arai, E., additional, Nagashio, R., additional, Fujimoto, H., additional, Hosoda, F., additional, Shibata, T., additional, Tsukamoto, T., additional, Yokoi, S., additional, Imoto, I., additional, Inazawa, J., additional, and Kanai, Y., additional
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- 2012
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9. Report of the Sixth International Workshop on Human Chromosome 11 Mapping 1998
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Gaudray, P., primary, Carle, G.F., additional, Gerhard, D.S., additional, Gessler, M., additional, Mannens, M.M., additional, Athanasiou, M., additional, Bliek, J., additional, Calender, A., additional, Debelenko, L.V., additional, Devignes, M.-D., additional, Evans, G.A., additional, Favier, R., additional, Forbes, S., additional, Gaudray, G., additional, Gawin, B., additional, Gordon, M., additional, Grimmond, S., additional, Grossfeld, P., additional, Harris, J., additional, Hattori, M., additional, Hosoda, F., additional, Hummerich, H., additional, James, M., additional, Kalla, J., additional, Katsanis, N., additional, Little, P., additional, Mattina, T., additional, Negrini, M., additional, Ohki, M., additional, Osborne Lawrence, S., additional, Parente, F., additional, Quincey, D., additional, Raynaud, S., additional, Reid, L., additional, Rethy, L.A., additional, Schuuring, E., additional, Sellar, G., additional, Stilgenbauer, S., additional, Talbot, C., additional, Taschner, P., additional, Thangarajah, T., additional, Tunnacliffe, A., additional, Turc-Carel, C., additional, van Heyningen, V., additional, Weber, G., additional, and Zabel, B., additional
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- 1999
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10. Escherichia coli dnaJ deletion mutation results in loss of stability of a positive regulator, CRP.
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Ohki, R, primary, Kawamata, T, additional, Katoh, Y, additional, Hosoda, F, additional, and Ohki, M, additional
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- 1992
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11. The isolation of CpG islands from human chromosomal regions 11q13 and Xp22 by segregation of partlymelted molecules.
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Shiraishi, M, Oates, A J, Li, X, Hosoda, F, Ohki, M, Alitalo, T, Lerman, L S, and Sekiya, T
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We isolated fragments containing parts of CpG islands from human chromosomal regions chosen for expected differences in gene density by segregation of partly melted molecules. Restriction fragments of P1 bacteriophage clones covering a region of 11q13 and those of cosmid clones derived from Xp22 were recovered from bands in denaturing gradient gels that were retained following prolonged exposure to electric field. Forty-five independent fragments derived from 11q13 and five from Xp22 were isolated. Nucleotide sequence analysis revealed that 11 of the 45 fragments from 11q13 contained CpG islands including four derived from known genes in 11q13. None of the five fragments derived from Xp22 resembled CpG islands. The number of CpG island fragments obtained was consistent with the expectation based on the number of Not I restriction endonuclease sites present at these regions. Adjustment of parameters in our quasi-theoretical approach to the rate of fragment dissociation improves the discrimination between retention and non-retention. The results support probable identification of CpG island fragments by their reduced rate of strand dissociation when retarded in a denaturing gradient gel.
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- 1998
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12. Report of the Sixth International Workshop on Human Chromosome 11 Mapping 1998. Nice, France, May 2-5, 1998
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Gaudray, P., Carle, G. F., Gerhard, D. S., Gessler, M., Mannens, M. M., Athanasiou, M., Bliek, J., Calender, A., Debelenko, L. V., Devignes, M., Evans, G. A., Favier, R., Forbes, S., Gaudray, G., Gawin, B., Gordon, M., Grimmond, S., Grossfeld, P., Harris, J., Hattori, M., Hosoda, F., Hummerich, H., James, M., Kalla, J., and Nicholas Katsanis
13. Sixth International Workshop on Human Chromosome 11 Mapping, Nice, Paris, 2-5 May, 1998
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Gaudray, P., Carle, G. F., Gerhard, D. S., Manfred Gessler, Mannens, M. M., Athanasiou, M., Bliek, J., Calender, A., Debelenko, L. V., Devignes, M. -D, Evans, G. A., Favier, R., Forbes, S., Gaudray, G., Gawin, B., Gordon, M., Grimmond, S., Grossfeld, P., Harris, J., Hattori, M., Hosoda, F., Hummerich, H., James, M., Kalla, J., Katsanis, N., Little, P., Mattina, T., Negrini, M., Ohki, M., Osborne Lawrence, S., Parente, F., Quincey, D., Raynaud, S., Reid, L., Rethy, L. A., Schuuring, E., Sellar, G., Stilgenbauer, S., Talbot, C., Taschner, P., Thangarajah, T., Tunnacliffe, A., Turc-Carel, C., Heyningen, V., Weber, G., Zabel, B., Human Genetics, ACS - Pulmonary hypertension & thrombosis, and ARD - Amsterdam Reproduction and Development
14. Deletion of the TNFAIP3/A20 gene detected by FICTION analysis in classical Hodgkin lymphoma
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Nomoto Junko, Hiramoto Nobuhiro, Kato Motohiro, Sanada Masashi, Maeshima Akiko, Taniguchi Hirokazu, Hosoda Fumie, Asakura Yoshitaka, Munakata Wataru, Sekiguchi Naohiro, Maruyama Dai, Watanabe Takashi, Nakagama Hitoshi, Takeuchi Kengo, Tobinai Kensei, Ogawa Seishi, and Kobayashi Yukio
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FICTION analysis ,Hodgkin lymphoma ,TNFAIP3 gene ,Homozygous deletion ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The TNFAIP3 gene, which encodes a ubiquitin-modifying enzyme (A20) involved in the negative regulation of NF-κB signaling, is frequently inactivated by gene deletions/mutations in a variety of B-cell malignancies. However, the detection of this in primary Hodgkin lymphoma (HL) specimens is hampered by the scarcity of Hodgkin Reed-Sternberg (HR-S) cells even after enrichment by micro-dissection. Methods We used anti-CD30 immunofluorescence with fluorescence in-situ hybridization (FISH) to evaluate the relative number of TNFAIP3/CEP6 double-positive signals in CD30-positive cells. Results From a total of 47 primary classical Hodgkin lymphoma (cHL) specimens, 44 were evaluable. We found that the relative numbers of TNFAIP3/CD30 cells were distributed among three groups, corresponding to those having homozygous (11%), heterozygous (32%), and no (57%) deletions in TNFAIP3. This shows that TNFAIP3 deletions could be sensitively detected using our chosen methods. Conclusions Comparing the results with mutation analysis, TNFAIP3 inactivation was shown to have escaped detection in many samples with homozygous deletions. This suggests that TNFAIP3 inactivation in primary cHL specimens might be more frequent than previously reported.
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- 2012
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15. Pan-cancer analysis of whole genomes
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Campbell, P. J. a., Abpemail, Author, Getz, G. b., C, D, Eemail, Author, Korbel, J. O. f., Gemail, Author, Stuart, hEmail Author, J. M., Jennings, J. L. i., Stein, J, L. D. k., Lemail, Author, Perry, M. D. m., Nahal-Bose, N, Ouellette, H. K. n., B. F. F. o., P, C. H. k., Li, Rheinbay, Q, E. b., E, Nielsen, R, Sgroi, G. P. r., D. C. r., Wu, C. -L. r., Faquin, W. C. r., Deshpande, V. r., Boutros, P. C. k., Q, S, Lazar, T, Hoadley, A. J. u., K. A. v., W, Louis, D. N. r., Dursi, L. J. k., Yung, X, Bailey, C. K. n., M. H. y., Z, Saksena, G. b., Raine, Abp, K. M., Buchhalter, Aa, I., Ab, Ac, Kleinheinz, Aa, K., Schlesner, Ac, Aa, M., Zhang, Ad, Wang, J. n., Ae, W., Wheeler, D. A., Af, Ding, Ag, L. y., Z, Simpson, Ah, J. T. k., Ai, O’Connor, B. D. n., Yakneen, Aj, Ellrott, S. g., Ak, K., Miyoshi, Al, N., Butler, Abp, A. P., Royo, Am, R., Shorser, S. I. k., Vazquez, Am, M., Rausch, An, Tiao, T. g., Waszak, G. b., Rodriguez-Martin, S. M. g., Ao, B., Ap, Aq, Shringarpure, Ar, S., D. -Y., As, Demidov, G. M., At, Au, Av, Delaneau, Aw, O., Ax, Ay, Hayashi, Al, S., Imoto, Habermann, N. g., Segre, A. V. b., Garrison, Az, Abp, E., Cafferkey, A. f., Alvarez, E. G., Ao, Heredia-Genestar, J. M., Ba, Muyas, At, F., Drechsel, At, O., Bruzos, Av, A. L., Ao, Temes, Ao, J., Zamora, Ap, Abp, Baez-Ortega, Bb, A., Kim, H. -L., Bc, Mashl, R. J. z., Bd, Ye, Be, K., Dibiase, Bf, Bg, A., Huang, K. -L. z., Letunic, Bh, Bi, I., Mclellan, M. D. y., Z, Ah, Newhouse, S. J. f., Shmaya, As, T., Kumar, Bj, S., Wedge, Bk, D. C., Bl, Abp, Bm, Wright, M. H., Ar, Yellapantula, V. D., Bn, Gerstein, Bo, Bj, M., Bk, Bp, Khurana, Bq, E., Br, Bs, Marques-Bonet, Bt, Bu, T., Bv, Bw, Navarro, Bx, Bu, A., Bustamante, C. D., Ar, Siebert, By, Bz, R., Nakagawa, Ca, Cb, H., Easton, D. F., Cc, Ossowski, Cd, At, S., Tubio, J. M. C., Ao, De La Vega, F. M., Ar, As, By, Estivill, At, X., Yuen, Ce, Mihaiescu, D. k., Omberg, G. L. n., Cf, L., Ferretti, V. n., Sabarinathan, Cg, Ch, R., Ci, Cj, Pich, Ch, O., Gonzalez-Perez, Cj, Ch, A., Taylor-Weiner, Cj, Ck, A., Fittall, M. W., Cl, Demeulemeester, Cl, J., Tarabichi, Cm, Cl, M., Abp, Roberts, Abp, N. D., Van, Loo, Cl, P., Cortés-Ciriano, Cm, Cn, I., Co, Cp, Urban, L. f., Park, G, Co, P., Zhu, Cp, Cq, B., Pitkänen, E. g., Abp, Y., Saini, Cr, N., Klimczak, L. J., Cs, Weischenfeldt, J. g., Ct, Cu, Sidiropoulos, Cu, N., Alexandrov, L. B., Cv, Abp, Rabionet, At, R., Av, Cw, Escaramis, At, G., Cx, Cy, Bosio, At, Av, Holik, A. Z., At, Susak, At, H., Prasad, Av, Av, A., Erkek, S. g., Calabrese, C. f., Raeder, G, Harrington, B. g., Cz, E., Mayes, Da, S., Turner, Da, D., Juul, Cz, S., Roberts, S. A., Db, Song, Cq, L., Koster, Dc, R., Mirabello, Hua, Cq, X., Tanskanen, T. J., Dd, Tojo, Aq, M., Chen, Bk, J., Aaltonen, De, L. A., Df, Rätsch, Dg, G., Dh, Di, Dj, Dk, Schwarz, Dl, R. F. f., Dm, Dn, Do, Butte, A. J., Dp, Brazma, A. f., Chanock, S. J., Cq, Chatterjee, Dq, N., Stegle, Dr, O. f., G, Harismendy, Ds, Dt, O., Bova, G. S., Du, Gordenin, D. A., Cr, Haan, D. h., Sieverling, Dv, L., Feuerbach, Dw, Chalmers, Dx, D., Joly, Dy, Y., Knoppers, Dy, B., Molnár-Gábor, Dz, F., Phillips, Dy, M., Thorogood, Dy, A., Townend, Dy, D., Goldman, Ea, M., Fonseca, N. A. f., Xiang, Eb, Craft, Q. n., Ea, B., Piñeiro-Yáñez, Ec, E., Muñoz, A. f., Petryszak, R. f., Füllgrabe, A. f., Al-Shahrour, Ec, F., Keays, M. f., Haussler, Ea, D., Weinstein, Ed, Ee, J., Huber, Ef, Valencia, W. g., Am, A., Papatheodorou, Bw, Zhu, I. f., Ea, J., Fan, Ae, Y., Torrents, Am, D., Bieg, Bw, Eg, M., Chen, Eh, Ei, K., Chong, Ej, Z., Cibulskis, K. b., Eils, Aa, R., Ac, Ek, Fulton, El, R. S. y., Z, Gelpi, Ah, J. L., Am, Gonzalez, Em, S. f., G, Gut, I. G., Av, Hach, Bu, En, F., Heinold, Eo, Ac, Hu, Ep, T., Huang, V. k., Hutter, Eh, B., Eq, Er, Jäger, Aa, N., Jung, Es, J., Ep, Y., Lalansingh, C. k., Leshchiner, I. b., Livitz, D. b., E. Z., Ep, Maruvka, Y. E. b., R, Et, Milovanovic, Nielsen, M. M., Eu, Paramasivam, Pedersen, Eh, J. S., Eu, Puiggròs, Ev, Sahinalp, S. C., Eo, Ew, Ex, Sarrafi, Eo, I., Stewart, Ex, Stobbe, C. b., M. D., Av, Wala, Bu, J. A. b., E, Wang, Ey, J. z., Be, Wendl, Ez, M. z., Fa, Werner, Fb, Aa, J., Fc, Wu, Ep, Z., Xue, Ep, H., Yamaguchi, T. N. k., Bn, V., Davis-Dusenbery, Bo, B. N., Fd, Grossman, R. L., Fe, Ff, Y., Heinold, Fg, M. C., Aa, Hinton, Ac, Abp, J., Jones, Abp, D. R., Menzies, Abp, A., Stebbings, Abp, L., Hess, J. M. b., Rosenberg, Et, M. b., R, Dunford, A. J. b., Gupta, M. b., Imielinski, Fh, M., Meyerson, Fi, M. b., E, Beroukhim, Ey, R. b., E, Reimand, Fj, J. k., Q, Dhingra, Br, P., Favero, Bt, Fk, F., Dentro, Bl, S., Abp, Cl, Wintersinger, Fl, J., Fm, Fn, Rudneva, V. g., Park, J. W., Fo, Hong, E. P., Fo, Heo, S. G., Fo, Kahles, Dg, A., Lehmann, K. -V., Dg, Di, Dj, Fp, Fq, Soulette, C. M., Aj, Shiraishi, Al, Y., Liu, Fr, F., Fs, He, Fr, Y., Demircioğlu, Ft, D., Davidson, Fu, N. R., Dg, Dl, Fp, Greger, L. f., Fv, S., Liu, Fw, Fv, D., Stark, Fw, S. G., Dj, Fp, Fx, Zhang, Fy, Amin, S. B., Fz, Ga, Gb, Bailey, Gc, P., Chateigner, A. n., Frenkel-Morgenstern, Gd, M., Hou, Fv, Y., Huska, Fw, M. R., Dm, Kilpinen, Ge, H., Lamaze, F. C. k., Fv, C., Fw, Li, Fv, X., Marin, Fw, M. G., Aj, Markowski, Dm, J., Nandi, Gf, T., Ojesina, A. I., Gg, Gh, Gi, Pan-Hammarström, Fv, Q., Park, Gj, P. J., Co, Pedamallu, Cp, C. S. b., E, Fj, Su, Fv, H., Tan, Fw, Gf, P., Gk, Gl, Teh, Gm, B. T., Gk, Gl, Gm, Gn, Go, Wang, Fv, J., Xiong, Fw, Ye, Yung, Fw, Zhang, C. n., Zheng, Fr, L., Zhu, Awadalla, Fw, P. k., L, Creighton, C. J., Gp, Fv, K., Yang, Fw, Göke, Ft, J., Zhang, Gq, Fr, Z., Brooks, Gr, A. N. b., Aj, Fittall, Ey, Martincorena, Abp, I., Rubio-Perez, Ch, C., Cj, Gs, Eu, M., Schumacher, S. b., Shapira, Gt, O. b., Ey, Tamborero, Ch, D., Mularoni, Cj, Ch, L., Hornshøj, Cj, Eu, H., Deu-Pons, Cj, J., Muiños, Gu, Ch, F., Bertl, Cj, Eu, J., Guo, Gv, Ev, Q., Gonzalez-Perez, Cj, Gw, Xiang, Gx, Q., Bazant, W. f., Barrera, E. f., Al-Sedairy, S. T., Gy, Aretz, Gz, A., Bell, Ha, C., Betancourt, Hb, M., Buchholz, Hc, C., Calvo, Hd, F., Chomienne, He, C., Dunn, Hf, M., Edmonds, Hg, S., Green, Hh, E., Gupta, Hi, S., C. M., Hh, Jegalian, Hj, K., Hk, N., Hl, Y., Hm, Hn, Nakagama, Ho, H., Nettekoven, Hp, G., Planko, Hp, L., Scott, Hk, D., Shibata, Hq, T., Shimizu, Hr, Hs, K., Stratton, Abp, M. R., Yugawa, Hs, T., Tortora, Ht, G., Vijayraghavan, Hu, Hi, K., Zenklusen, J. C., Hv, Hw, D., B. M., Dy, Aminou, B. n., Bartolome, Am, J., Boroevich, K. A., Cb, Boyce, Hx, Buchanan, R. f., Ak, A., Byrne, N. J. n., Hy, Z., Cho, Hz, S., Choi, Ia, W., Clapham, Abp, P., Dow, M. T., Hy, Eils, X, Ek, J., Farcas, El, Hy, C., Fayzullaev, N. n., Flicek, P. f., Heath, A. P., Ib, Hofmann, Ic, O., J. H., Id, Hudson, T. J., Ie, Hübschmann, If, Ac, D., Do, Ek, Ig, Ih, Ivkovic, Ii, S., Jeon, S. -H., Ia, Jiao, W. k., Kabbe, Dj, Fq, Kerssemakers, J. N. A., Aa, Ia, H., Ij, J., Koscher, Ik, M., Koures, Hy, A., Kovacevic, Ii, M., Lawerenz, El, C., Il, J., Mijalkovic, Mijalkovic-Lazic, A. M., Ii, Miyano, Nastic, Nicholson, Ocana, D. f., Ohi, Al, K., Ohno-Machado, Hy, L., Pihl, T. D., Im, Prinz, Radovic, Ii, P., Short, C. f., Sofia, H. J., Hh, Spring, Fe, J., Struck, A. J., Ak, Tijanic, Ii, N., Vicente, Hv, Z., Williams, Woo, Ia, Y., Wright, A. J. k., Yang, Hv, L., Hamilton, M. P., In, Johnson, T. A., Hx, Kahraman, Io, A., Ip, Iq, Kellis, M. b., Polak, Ir, P. b., C, Sallari, E, Sinnott-Armstrong, R. b., N. b., Ar, Von, Mering, Iq, C., Beltran, Is, Av, S., Gerhard, Bu, D. S., It, Av, M., Trotta, Bu, J. -R., Bu, Whalley, J. P., Bu, Niu, Iu, B., Espiritu, S. M. G. k., Gao, Ez, Y., Lalansingh, Iv, Teague, C. M. k., Abp, J. W., Wendl, M. C. z., Fa, Fb, Abascal, Abp, F., Bader, G. D. l., Bandopadhayay, P. b., Iw, Ix, Barenboim, J. k., Brunak, Iy, S., Carlevaro-Fita, Iz, Ja, J., Jb, Jc, Chakravarty, Jd, D., Chan, Je, C. W. Y., Aa, Choi, Dw, J. K., Jf, Diamanti, Jg, K., Fink, Frigola, Jh, Gu, J., Gambacorti-Passerini, Ji, C., Garsed, D. W., Jj, Haradhvala, N. J. b., Harmanci, R, A. O., Bk, Helmy, Jk, Fm, M., Herrmann, Aa, C., Ac, Jl, Hobolth, Ev, A., Hodzic, Gv, Ex, E., Dv, C., Isaev, Dw, K. k., Q, Izarzugaza, J. M. G., Iy, Jb, R., Juul, Jm, R. I., Eu, Kim, J. b., J. K., Jn, Jan, Komorowskijg, Lanzós, Jo, Jb, A., Jc, Jm, Larsson, Dg, E., Lee, Bk, D., Bk, S., Bk, X., Lin, Z. b., Liu, Jp, E. M., Br, Bt, Jq, Lochovsky, Bj, L., Bk, Gb, Lou, Madsen, Bk, Eu, T., Marchal, Jr, K., Martinez-Fundichely, Js, Br, A., Bs, Bt, Mcgillivray, P. D., Bj, Meyerson, Bk, W., Paczkowska, Jt, Park, M. k., Ju, K., Park, Jv, Jw, K., Pons, Jx, T., Pulido-Tamayo, Jr, S., Reyes-Salazar, Js, Ch, I., Reyna, M. A., Jy, Rubin, M. A., Jm, Jz, Ka, Kb, Kc, Salichos, Sander, Bk, Dg, C., Ey, Kd, Schumacher, Ke, S. E. b., Gt, Shackleton, Jj, M., Shen, Ke, C., Shrestha, Kf, Eo, R., Shuai, S. k., Tsunoda, L, Hx, T., Kg, Kh, Umer, Ki, H. M., Jg, Uusküla-Reimand, Kj, Kk, L., Verbeke, Kl, L. P. C., Js, Wadelius, Km, Kn, C., Wadi, L. k., Warrell, Bj, J., Bk, Wu, Ko, G., Kp, J., Zhang, Ez, X., Zhang, Kq, Bk, Y., Kr, Ks, Zhao, Kt, Z., Zou, Ku, L., Lawrence, M. S. b., R, Hx, Raphael, B. J., Jy, P. J., Gc, Craft, D. b., Goldman, Kv, M. J., Ea, Aburatani, Kw, H., Binder, Kx, H., Dinh, Ky, H. Q., Kz, S. C., Av, Hoffmann, Bu, Kx, S., Ky, La, Imbusch, Lb, C. D., Dv, Kretzmer, Ky, H., Laird, Lb, P. W., Lc, Martin-Subero, J. I., Bw, Nagae, Ld, Kw, G., Shen, Le, Lf, H., Ik, Q., Weichenhan, Lg, D., Zhou, Lf, W., Berman, B. P., Kz, Lh, Li, Brors, Dv, B., Er, Lj, Plass, Lg, C., Akdemir, K. C., Ei, Bowtell, D. D. L., Jj, Burns, K. H., Lk, Busanovich, Ll, J. b., Lm, Chan, Ln, K., Dueso-Barroso, Edwards, P. A., Lo, Etemadmoghadam, Lp, Jj, D., Haber, J. E., Lq, D. T. W., Lr, Ls, Ju, Y. S., Jf, Abp, Kazanov, M. D., Lt, Lu, Lv, Koh, Lw, Y., Kumar, Lx, Lee, K. b., E. A., Ly, J. J. -K., Co, Lynch, Cp, A. G., Lo, Lp, Lz, Macintyre, Lo, G., Markowetz, Lo, F., Navarro, Lp, F. C. P., Bj, Pearson, J. V., Ma, Rippe, Mb, Do, K., Scully, Mc, R., Villasante, Am, I., Waddell, Ma, N., Yang, Mb, Md, L., Yao, Fh, X., Yoon, Me, S. -S., Lx, C. -Z. b., E, Ey, Bergstrom, E. N., Mf, Boot, Gl, A., Covington, Mg, Ag, K., Fujimoto, Cb, A., M. N., Gl, Islam, Mg, S. M. A., Cv, Mcpherson, J. R., Gl, Morganella, Mg, Abp, S., Mustonen, Mh, V., Mi, Mj, A. W. T., Mk, Prokopec, S. D. k., Vázquez-García, Bn, I., Ml, Mm, Abp, Wu, Gl, Y., Yousif, Mg, F. k., Yu, Mn, W., Rozen, S. G., Gl, Gm, Mg, Rudneva, V. A. g., S. S., Ar, D. J., Da, Xia, Mo, T., Atwal, G. k., L, Fn, Chang, D. K., Gc, Cooke, Mp, S. L., Gc, Faltas, B. M., Dl, Haider, S. k., Kaiser, V. B., Mq, Karlić, Mr, R., Kato, Ms, M., Kübler, K. b., E, R, Margolin, Martin, Mt, S., Abp, Nik-Zainal, Mu, S., Mv, Mw, Abp, P’Ng, Semple, C. k., C. A., Mq, Smith, Ak, J., Sun, R. X. k., Thai, K. n., D. W., Mx, Yuan, My, Lo, K., Mt, Mz, Biankin, A. V., Gc, Mp, Na, Garraway, Nb, Ey, L., Grimmond, S. M., Nc, Adams, Abp, D. J., Anur, Nd, P., Cao, Ae, S., Christie, E. L., Jj, Cmero, Ne, M., Nf, Ng, Cun, Nh, Y., Dawson, Abp, K. J., S. C., Bl, Deshwar, A. G., Ni, Donmez, Eo, N., Drews, Ex, R. M., Lo, Gerstung, M. f., G, Ha, Haase, G. b., Cl, K., Jerman, L. g., Nj, Ji, Nk, Y., Jolly, Nl, Cl, C., Nm, J., Lee-Six, Abp, H., Malikic, Eo, S., Mitchell, Ex, T. J., Lp, Abp, Nn, Morris, Q. D., Fn, Oesper, No, Np, L., Peifer, Nh, M., Peto, Nq, M., Rosebrock, D. b., Rubanova, Ai, Y., Salcedo, Fn, Sengupta, A. k., Nr, S., Shi, No, R., Shin, S. J., Fy, Spiro, O. b., Vembu, No, S., Wintersinger, Ns, J. A., Fl, T. -P., Nh, Nt, K., Nu, H., Spellman, Nv, P. T., Nw, Weinstein, J. N., Ee, Chen, Ef, Fujita, Cb, M., Han, Kq, L., Hasegawa, Al, T., Komura, Al, M., Ae, J., Mizuno, Nx, S., Shimizu, Al, E., Ny, Xu, Nz, Y., Yamaguchi, Al, R., No, F., Kq, Y., Yoon, C. J., Jf, Yuan, Liang, Ae, H., Alawi, Oa, M., Borozan, Ob, Brewer, I. k., D. S., Oc, Cooper, Od, C. S., Od, Oe, Of, Desai, N. n., Grundhoff, Oa, A., Iskar, Og, Oh, M., Oi, X., Zapatka, Lichter, Eq, P., Alsop, Oh, Jj, K., Bruxner, T. J. C., Jh, Christ, A. N., Jh, Cordner, S. M., Oj, Cowin, P. A., Ok, Drapkin, Ol, R., Fereday, Ok, S., George, Gb, J., Ok, A., Holmes, Ma, O., Hung, Mb, J. A., Om, Kassahn, On, K. S., Jh, Kazakoff, Oo, S. H., Ma, Kennedy, Mb, C. J., Op, Leonard, Oq, C. R., Ma, Mileshkin, Mb, Jj, L., Miller, D. K., Jh, Mp, Or, Arnau, G. M., Ok, Mitchell, Ok, C., Newell, Ma, F., Nones, Mb, Ma, K., Patch, Mb, A. -M., Ma, Quinn, Mb, M. C., Ma, Taylor, Mb, D. F., Jh, Thorne, Ok, H., Traficante, Ok, N., Vedururu, Ok, R., N. M., Mb, Waring, P. M., Os, Wood, Ma, S., Mb, Xu, Ma, Q., Defazio, Mb, Ot, A., Ou, Ov, Anderson, M. J., Jh, Antonello, Ow, D., Barbour, A. P., Ox, Bassi, Oy, Ow, C., Bersani, Oz, S., Cataldo, Oz, I., Chantrill, Pa, L. A., Mp, Chiew, Pb, Y. -E., Ot, Chou, Mp, A., Cingarlini, Pc, Ht, S., Cloonan, Pd, N., Corbo, Pa, V., Davi, Pe, M. V., Pf, Duthie, F. R., Gc, Gill, Pg, A. J., Mp, Graham, Pc, J. S., Gc, Harliwong, Ph, Jh, I., Jamieson, N. B., Gc, Nb, Pi, Johns, A. L., Mp, Kench, Or, J. G., Mp, Pc, Pj, Landoni, Ow, L., Lawlor, R. T., Pa, Mafficini, Pa, A., Merrett, N. D., Ow, Miotto, Pk, Ow, M., Musgrove, E. A., Gc, Nagrial, A. M., Mp, Oien, K. A., Os, Pajic, Pl, Mp, M., Pinese, Pm, M., Robertson, A. J., Jh, Rooman, Mp, I., Rusev, B. C., Pa, Samra, J. S., Ow, Scardoni, Pc, Oz, M., Scarlett, C. J., Mp, Scarpa, Pn, Sereni, Ow, E., Sikora, K. O., Pa, Simbolo, Pe, M., Taschuk, M. L. n., Toon, C. W., Mp, Vicentini, Pa, C., Mp, J., Zeps, Po, N., Behren, Pp, Pq, A., Burke, Pr, H., Cebon, Pq, J., Dagg, R. A., Ps, Paoli-Iseppi, De, Pt, R., Dutton-Regester, Field, M. A., Pu, Fitzgerald, Pv, A., Hersey, Pr, P., Jakrot, Pr, V., Johansson, P. A., Ma, Kakavand, Pt, H., Kefford, R. F., Pw, Lau, L. M. S., Px, Long, G. V., Py, Pickett, H. A., Px, Pritchard, A. L., Ma, Pupo, G. M., Pz, Saw, R. P. M., Py, Schramm, S. -J., Qa, Shang, C. A., Pv, Py, P., Spillane, A. J., Py, Stretch, J. R., Py, Tembe, Ot, V., Thompson, Qa, J. F., Py, Vilain, R. E., Qb, Wilmott, J. S., Py, J. Y., Qc, Hayward, N. K., Ma, Mann, Pr, G. J., Ot, Scolyer, Qd, R. A., Ou, Py, Qb, Bartlett, Qe, Qf, J., Bavi, Qg, Qh, P., Chadwick, D. E., Qi, Chan-Seng-Yue, Qh, M., Cleary, Qh, S., Connor, Qj, A. A., Qj, Czajka, Qk, If, K., Denroche, R. E., Qh, Dhani, N. C., Ql, Eagles, If, J., Gallinger, Qj, Qk, Grant, R. C., Qh, Hedley, Qk, Ql, D., Hollingsworth, M. A., Qm, Jang, G. H., Qh, Kalimuthu, S. -B., Qn, Lungu, Qh, I., Luo, Qo, Mbabaali, X. k., If, F., T. A., Qk, J. K., If, Moore, M. J., Ql, Notta, Qh, F., Pasternack, Qp, If, D., Petersen, G. M., Qq, Roehrl, M. H. A. q., Qh, Qr, Qs, Qt, Sam, If, M., Selander, Qk, I., Serra, Os, S., Shahabi, Qn, S., Thayer, S. P., Qm, Timms, L. E., If, Wilson, G. W. k., Wilson, Qh, J. M., Qh, Wouters, B. G., Qu, J. D., If, Qh, Qv, Beck, T. A. n., Bhandari, Qw, Collins, V. k., C. C., Eo, Fleshner, N. E., Qx, Fox, N. S. k., Fraser, M. k., Heisler, L. E., Qy, Lalonde, E. k., Livingstone, J. k., Meng, Qz, A., Sabelnykova, V. Y. k., Shiah, Y. -J. k., Van der Kwast, Ra, T., Bristow, R. G. q., Rb, Rc, Rd, Re, Ding, Rf, S., Rg, D., Fv, L., Nie, Rg, Y., Xiao, Rh, Xing, Hm, R., Yang, Ri, Rj, Y., Banks, R. E., Rk, Bourque, Rl, G., Brennan, Rm, Rn, P., Letourneau, Ro, L., Riazalhosseini, Rm, Y., Scelo, Rn, G., Vasudev, Rk, N., Viksna, Rp, Rq, J., Lathrop, Rm, M., Tost, Rr, J., Ahn, S. -M., Rs, Aparicio, Rt, S., Arnould, Ru, L., Aure, M. R., Rv, Bhosle, Abp, S. G., Birney, E. f., Borg, Rw, A., Boyault, Rx, S., Brinkman, A. B., Ry, Brock, J. E., Rz, Broeks, Sa, A., Børresen-Dale, A. -L., Rv, Caldas, Sb, C., Chin, Sc, S. -F., Sb, Davies, Sc, Mu, H., Abp, Mv, Desmedt, Sd, C., Dirix, Se, Sf, L., Dronov, Ehinger, Sg, A., Eyfjord, J. E., Sh, Fatima, Gt, A., Foekens, J. A., Si, Futreal, P. A., Sj, Garred, Sk, Ø., Giri, Sl, D. D., Sm, Glodzik, Abp, D., Grabau, Sn, D., Hilmarsdottir, Sh, H., Hooijer, G. K., So, Jacquemier, Sp, J., S. J., Sq, Jonasson, J. G., Sh, Jonkers, Sr, J., H. -Y., Sp, King, T. A., Ss, Knappskog, St, Su, S., Abp, Kong, Sp, G., Krishnamurthy, Sv, S., Lakhani, S. R., Sw, Langerød, Rv, A., Larsimont, Sx, D., H. J., Sq, J. -Y., Sy, M. T. M., Sj, Lingjærde, O. C., Sz, Macgrogan, Ta, G., Martens, J. W. M., Si, O’Meara, Pauporté, He, I., Pinder, Tb, S., Pivot, Tc, X., Provenzano, Td, E., Purdie, C. A., Te, Ramakrishna, Abp, M., Ramakrishnan, Abp, K., Reis-Filho, Sm, J., Richardson, A. L., Gt, Ringnér, Rw, M., Rodriguez, J. B., Am, Rodríguez-González, F. G., Iz, Romieu, Tf, G., Salgado, Os, R., Sauer, Sz, T., Shepherd, Abp, R., Sieuwerts, A. M., Si, Simpson, P. T., Sw, Smid, Si, M., Sotiriou, Span, P. N., Tg, Stefánsson, Ó. A., Th, Stenhouse, Ti, A., Stunnenberg, H. G., Fw, Sweep, Tj, Tk, F., Tan, B. K. T., Tl, Thomas, Tm, G., Thompson, A. M., Ti, Tommasi, Tn, S., Treilleux, To, I., Tutt, Tp, Ueno, N. T., Nv, Van, Laere, Sf, S., Van den Eynden, G. G., Sf, Vermeulen, Sf, P., Viari, Vincent-Salomon, Tj, A., Wong, B. H., Tq, Yates, Abp, X., Van, Deurzen, C. H. M., Tr, van de Vijver, M. J., Os, Van’T, Veer, Ts, L., Ammerpohl, Tt, O., Tu, Tv, Aukema, Tu, S., Tv, Tw, Bergmann, A. K., Tx, Bernhart, S. H., Kx, Ky, Lb, Borkhardt, Ty, A., Borst, Tz, C., Burkhardt, Ua, B., Claviez, Ub, A., Goebler, M. E., Uc, Haake, Tt, A., Haas, Tz, S., Hansmann, Ud, M., Hoell, J. I., Ty, Hummel, Ue, M., Karsch, Uf, D., Klapper, Tw, W., Kneba, Uf, M., Kreuz, Ug, M., Kube, Uh, D., Küppers, Ui, R., Lenze, Ue, D., Loeffler, López, Ca, C., Mantovani-Löffler, Tt, Uj, L., Möller, Uk, P., Ott, Ul, G., Radlwimmer, Oh, B., Richter, Tt, J., Rohde, Tw, Um, M., Rosenstiel, P. C., Un, Rosenwald, Uo, A., Schilhabel, M. B., Un, Schreiber, Up, S., Stadler, P. F., Kx, Staib, Uq, P., Stilgenbauer, Ur, S., Sungalee, S. g., Szczepanowski, Tw, M., Toprak, U. H., Ac, Trümper, Us, L. H. P., Uh, Wagener, Ca, R., Zenz, Tt, Er, T., Hovestadt, Oh, V., Von, Kalle, Do, C., Kool, Korshunov, Lr, Ik, A., Landgraf, Ut, P., Lehrach, Uu, Uv, H., Northcott, P. A., Uw, Pfister, S. M., Ik, Lr, Ux, Reifenberger, Uu, G., Warnatz, H. -J., Uv, Wolf, Uy, S., Yaspo, M. -L., Uv, Assenov, Uz, Y., Gerhauser, Minner, Va, S., Schlomm, Ct, T., Simon, Vb, Vc, R., Sauter, Vc, G., Sültmann, Er, H., Biswas, Vd, N. K., Ve, Maitra, Ve, A., Majumder, P. P., Ve, Sarin, Vf, R., Barbi, Pe, S., Bonizzato, Pa, G., Cantù, Dei, Tos, A. P., Vg, Fassan, Vh, M., Grimaldi, Pa, S., Luchini, Oz, C., Malleo, Ow, G., Marchegiani, Milella, Michele, Ht, M., Paiella, Ow, S., Pea, Ow, A., Pederzoli, Ow, P., Ruzzenente, Salvia, Ow, R., Sperandio, Pa, N., Arai, Hq, Y., Hama, Hq, N., Hiraoka, Vi, N., Hosoda, Hq, F., Nakamura, Hq, H., Ojima, Vj, H., Okusaka, Vk, T., Totoki, Urushidate, Hr, T., Fukayama, Vl, M., Ishikawa, Vm, S., Katai, Vn, H., Katoh, Vm, H., Vm, D., Rokutan, Ms, H., Saito-Adachi, Suzuki, Kw, A., Taniguchi, Vo, Vp, H., Tatsuno, Kw, K., Ushiku, Vl, T., Yachida, Hq, S., Yamamoto, Vq, Kw, S., Aikata, Vr, H., Arihiro, Vr, K., Ariizumi, S. -I., Vs, Chayama, Furuta, Gotoh, Vt, K., Hayami, Vu, S., Hirano, Vv, S., Kawakami, Vr, Y., Maejima, Cb, K., Vv, T., Nakano, Ohdan, Sasaki-Oku, Tanaka, Al, H., Vu, M., Yamamoto, Vs, M., Yamaue, Vu, H., Choo, S. P., Vw, Cutcutache, Gl, I., Khuntikeo, Mg, Ow, N., Ong, Vx, C. K., Vy, Pairojkul, Os, C., Popescu, Vz, I., K. S., Wa, Aymerich, Wb, M., Lopez-Guillermo, Wc, A., López-Otín, Wd, C., Puente, X. S., Wd, Campo, We, E., Amary, Wf, Wg, F., Baumhoer, Wh, D., Behjati, Bjerkehagen, Wh, B., Futreal, Wi, Myklebost, Su, O., Pillay, Wj, N., Tarpey, Wk, P., Tirabosco, Wl, R., Zaikova, Wm, O., Flanagan, A. M., Wn, Boultwood, Wo, J., Bowen, Abp, D. T., Cazzola, Wp, M., A. R., Lp, Hellstrom-Lindberg, Wq, E., Malcovati, Wp, L., Nangalia, Wr, J., Papaemmanuil, Vyas, Ma, P., Ang, Ws, Wt, Y., Barr, Wu, H., Beardsmore, Wv, D., Eldridge, Lo, M., Gossage, Ww, J., Grehan, Mv, N., Hanna, G. B., Wx, Hayes, S. J., Wy, Hupp, Wz, T. R., Xa, Khoo, Xb, D., Lagergren, Wq, J., Lovat, Xc, L. B., Ge, Macrae, Ee, S., O’Donovan, Mv, M., O’Neill, J. R., Xd, Parsons, S. L., Xe, Preston, S. R., Xf, Puig, Xg, S., Roques, Xh, T., Sanders, G. w., Sothi, Xi, S., Tavaré, Lo, S., Tucker, Xj, O., Turkington, Xk, R., Underwood, T. J., Xl, Welch, Xm, I., R. C., Mv, Berney, D. M., Xn, Bono, De, J. S., Oe, Cahill, Xo, D., Camacho, Oe, N., Dennis, N. M., Xo, Dudderidge, Xo, T., Edwards, Xp, S. E., Oe, Fisher, Xo, C., Foster, C. S., Xq, Ghori, Xr, Gill, Ws, P., Gnanapragasam, V. J., Nn, Gundem, Xs, Jq, G., Hamdy, F. C., Xt, Hawkins, Hazell, Xo, S., Howat, Nn, W., Isaacs, W. B., Xu, Karaszi, Ws, K., Kay, J. D., Ge, Xo, V., Kote-Jarai, Oe, Z., Kremeyer, Abp, B., Xo, P., Lambert, Ws, A., Leongamornlert, D. A., Oe, Abp, Livni, Xo, N., Y. -J., Xn, Luxton, Xv, H. J., Ge, Marsden, Ws, L., Massie, C. E., Lo, Matthews, Oe, L., Mayer, Xo, E., Mcdermott, Xw, Abp, U., Merson, Oe, S., Neal, D. E., Lo, Nn, Ng, Xx, A., Nicol, Ogden, Rowe, E. W., Xo, Shah, N. C., Nn, Xo, A., Verrill, Ws, C., Visakorpi, Xy, Du, T., Warren, A. Y., Nn, Whitaker, Xz, H. C., Ge, Xv, H., Van, As, Eeles, R. A., Oe, Abeshouse, Xo, Jq, A., Agrawal, Fe, N., Akbani, Mv, R., Al-Ahmadie, Ya, Jq, H., Albert, Qg, M., Aldape, Oi, K., Ally, Yb, Yc, A., Appelbaum, E. L. z., Armenia, Ge, Yd, J., Asa, Xe, S., Auman, Ye, J. T., Yf, Balasundaram, Yc, M., Balu, S. w., Barnholtz-Sloan, Yg, J., Bathe, Yh, O. F., Yi, Baylin, Yj, S. B., Dr, Benz, Xp, Yk, C., Berchuck, Yl, A., Berrios, Ym, M., Bigner, Yn, D., Birrer, M. r., Bodenheimer, T. w., Boice, Xg, L., Bootwalla, M. S., Ym, Bosenberg, Yo, M., Bowlby, Yc, R., Boyd, Yp, J., Broaddus, R. R., Oi, Yq, M., Brooks, Yc, D., Bullman, S. b., Caesar-Johnson, Fj, S. J., Hv, Carey, T. E., Yr, Carlsen, Cerfolio, Ys, R., Chandan, V. S., Yt, H. -W., Wt, Cherniack, Yd, A. D. b., Ey, Chien, Fj, Yu, J., Cho, J. b., Chuah, Yc, E., Cibulskis, C. b., Cope, Yv, L., Cordes, M. G. z., Curley, Xh, Yw, E., Czerniak, Oi, B., Danilova, Xb, Davis, I. J., Yx, Defreitas, T. b., Demchok, J. A., Hv, Dhalla, Yc, N., Dhir, Yy, R., Doddapaneni, H. V., Ag, El-Naggar, Oi, A., Felau, Xb, Hv, I., Ferguson, M. L., Yz, Finocchiaro, Za, G., Fong, K. M., Zb, Frazer, S. b., Friedman, Zc, W., Fronick, C. C. z., Fulton, Xh, Gabriel, L. A. z., Gao, S. B. b., Gehlenborg, N. b., Gershenwald, Zd, J. 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B., Xg, Tsao, Xe, M., Umbricht, Ye, Lk, C., Abg, Wv, Van Den Berg, D. J., Ym, Van, Meir, Abh, E. G., Veluvolu, U. v., Voet, D. b., Weinberger, Abi, P., Weisenberger, Wigle, Abj, D., Wilkerson, M. D. v., Wilson, R. K. z., Abk, Winterhoff, Abl, B., Wiznerowicz, Abm, M., Abn, Wong, T. z., Yc, Abo, W., Yau, Zhang, H. b., Yd, H., Hv, J., The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium View Correspondence (jump link), Medical Oncology, Pathology, IBM, Pharmacyclics, Novartis, Celgene, AstraZeneca, Bayer, Janssen Biotech, University of Chicago, Ipsen, Pfizer, Ono Pharmaceutical, Ariad Pharmaceuticals, Gilead Sciences, Bristol-Myers Squibb, University of St Andrews. School of Medicine, University of St Andrews. Statistics, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, RS: CAPHRI - R4 - Health Inequities and Societal Participation, Metamedica, Háskóli Íslands, University of Iceland, Faculty of Medicine, University of Helsinki, Department of Medical and Clinical Genetics, Research Programs Unit, Lauri Antti Aaltonen / Principal Investigator, ATG - Applied Tumor Genomics, Helsinki Institute of Life Science HiLIFE, Organismal and Evolutionary Biology Research Programme, Helsinki Institute for Information Technology, Institute of Biotechnology, Bioinformatics, Department of Computer Science, STEMM - Stem Cells and Metabolism Research Program, Centre of Excellence in Stem Cell Metabolism, Genome-Scale Biology (GSB) Research Program, Department of Physics, HUS Helsinki and Uusimaa Hospital District, University of Zurich, ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, Apollo - University of Cambridge Repository, Graduate School, Laboratory Genetic Metabolic Diseases, AGEM - Endocrinology, metabolism and nutrition, 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C, Malleo, G, Marchegiani, G, Milella, M, Paiella, S, Pea, A, Pederzoli, P, Ruzzenente, A, Salvia, R, Sperandio, N, Arai, Y, Hama, N, Hiraoka, N, Hosoda, F, Nakamura, H, Ojima, H, Okusaka, T, Totoki, Y, Urushidate, T, Fukayama, M, Ishikawa, S, Katai, H, Katoh, H, Komura, D, Rokutan, H, Saito-Adachi, M, Suzuki, A, Taniguchi, H, Tatsuno, K, Ushiku, T, Yachida, S, Yamamoto, S, Aikata, H, Arihiro, K, Ariizumi, S, Chayama, K, Furuta, M, Gotoh, K, Hayami, S, Hirano, S, Kawakami, Y, Maejima, K, Nakamura, T, Nakano, K, Ohdan, H, Sasaki-Oku, A, Tanaka, H, Ueno, M, Yamamoto, M, Yamaue, H, Choo, S, Cutcutache, I, Khuntikeo, N, Ong, C, Pairojkul, C, Popescu, I, Ahn, K, Aymerich, M, Lopez-Guillermo, A, Lopez-Otin, C, Puente, X, Campo, E, Amary, F, Baumhoer, D, Behjati, S, Bjerkehagen, B, Myklebost, O, Pillay, N, Tarpey, P, Tirabosco, R, Zaikova, O, Flanagan, A, Boultwood, J, Bowen, D, Cazzola, M, Green, A, Hellstrom-Lindberg, E, Malcovati, L, Nangalia, J, Papaemmanuil, E, Vyas, P, Ang, Y, Barr, H, Beardsmore, D, Eldridge, M, Gossage, J, Grehan, N, Hanna, G, Hayes, S, Hupp, T, Khoo, D, Lagergren, J, Lovat, L, Macrae, S, O'Donovan, M, O'Neill, J, Parsons, S, Preston, S, Puig, S, Roques, T, Sanders, G, Sothi, S, Tavare, S, Tucker, O, Turkington, R, Underwood, T, Welch, I, Fitzgerald, R, Berney, D, De Bono, J, Cahill, D, Camacho, N, Dennis, N, Dudderidge, T, Edwards, S, Fisher, C, Foster, C, Ghori, M, Gill, P, Gnanapragasam, V, Gundem, G, Hamdy, F, Hawkins, S, Hazell, S, Howat, W, Isaacs, W, Karaszi, K, Kay, J, Khoo, V, Kote-Jarai, Z, Kremeyer, B, Kumar, P, Lambert, A, Leongamornlert, D, Livni, N, Luxton, H, Marsden, L, Massie, C, Matthews, L, Mayer, E, Mcdermott, U, Merson, S, Neal, D, Nicol, D, Ogden, C, Rowe, E, Shah, N, Thomas, S, Verrill, C, Visakorpi, T, Warren, A, Whitaker, H, Zhang, H, van As, N, Eeles, R, Abeshouse, A, Agrawal, N, Akbani, R, Al-Ahmadie, H, Albert, M, Aldape, K, Ally, A, Appelbaum, E, Armenia, J, Asa, S, Auman, J, Balasundaram, M, Balu, S, Barnholtz-Sloan, J, Bathe, O, Baylin, S, Benz, C, Berchuck, A, Berrios, M, Bigner, D, Birrer, M, Bodenheimer, T, Boice, L, Bootwalla, M, Bosenberg, M, Bowlby, R, Boyd, J, Broaddus, R, Brock, M, Brooks, D, Bullman, S, Caesar-Johnson, S, Carey, T, Carlsen, R, Cerfolio, R, Chandan, V, Chen, H, Cherniack, A, Chien, J, Cho, J, Chuah, E, Cibulskis, C, Cope, L, Cordes, M, Curley, E, Czerniak, B, Danilova, L, Davis, I, Defreitas, T, Demchok, J, Dhalla, N, Dhir, R, Doddapaneni, H, El-Naggar, A, Felau, I, Ferguson, M, Finocchiaro, G, Fong, K, Frazer, S, Friedman, W, Fronick, C, Fulton, L, Gabriel, S, Gao, J, Gehlenborg, N, Gershenwald, J, Ghossein, R, Giama, N, Gibbs, R, Gomez, C, Govindan, R, Hayes, D, Hegde, A, Heiman, D, Heins, Z, Hepperla, A, Holbrook, A, Holt, R, Hoyle, A, Hruban, R, Hu, J, Huntsman, D, Huse, J, Iacobuzio-Donahue, C, Ittmann, M, Jayaseelan, J, Jefferys, S, Jones, C, Jones, S, Juhl, H, Kang, K, Karlan, B, Kasaian, K, Kebebew, E, Korchina, V, Kundra, R, Lai, P, Lander, E, Le, X, Levine, D, Lewis, L, Ley, T, Li, H, Lin, P, Linehan, W, Lype, L, Ma, Y, Maglinte, D, Mardis, E, Marks, J, Marra, M, Matthew, T, Mayo, M, Mccune, K, Meier, S, Meng, S, Mieczkowski, P, Mikkelsen, T, Miller, C, Mills, G, Moore, R, Morrison, C, Mose, L, Moser, C, Mungall, A, Mungall, K, Mutch, D, Muzny, D, Myers, J, Newton, Y, Noble, M, O'Donnell, P, O'Neill, B, Ochoa, A, Parker, J, Pass, H, Pastore, A, Pennell, N, Perou, C, Petrelli, N, Potapova, O, Rader, J, Ramalingam, S, Rathmell, W, Reuter, V, Reynolds, S, Ringel, M, Roach, J, Roberts, L, Sadeghi, S, Saller, C, Sanchez-Vega, F, Schadendorf, D, Schein, J, Schmidt, H, Schultz, N, Seethala, R, Senbabaoglu, Y, Shelton, T, Shi, Y, Shih, J, Shmulevich, I, Shriver, C, Signoretti, S, Simons, J, Singer, S, Sipahimalani, P, Skelly, T, Smith-McCune, K, Socci, N, Soloway, M, Sood, A, Tam, A, Tan, D, Tarnuzzer, R, Thiessen, N, Thompson, R, Thorne, L, Tsao, M, Umbricht, C, Van Den Berg, D, Van Meir, E, Veluvolu, U, Voet, D, Wang, L, Weinberger, P, Weisenberger, D, Wigle, D, Wilkerson, M, Wilson, R, Winterhoff, B, Wiznerowicz, M, Wong, T, Wong, W, Xi, L, Yau, C, Consortium, ICGC/TCGA Pan-Cancer Analysis of Whole Genomes, Demeulemeester, Jonas, Desmedt, Christine, Van Loo, Peter, Barcelona Supercomputing Center, Imperial College Healthcare NHS Trust- BRC Funding, Cancer Research UK, Basic (bio-) Medical Sciences, and Laboratory for Medical and Molecular Oncology
- Subjects
Male ,tert promoter mutations ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,DNA Mutational Analysis ,Normal tissue ,systematic analysis ,Germline ,Transcriptome ,0302 clinical medicine ,Aetiology ,Càncer ,Cellular Senescence ,Cancer ,0303 health sciences ,dna-damage ,Massive parallel sequencing ,Pan cancer ,REARRANGEMENTS ,High-Throughput Nucleotide Sequencing ,Genomics ,Sciences bio-médicales et agricoles ,Telomere ,COMPREHENSIVE ,3. Good health ,TERT PROMOTER MUTATIONS ,signatures ,030220 oncology & carcinogenesis ,Science & Technology - Other Topics ,Erfðarannsóknir ,Human ,Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC] ,Evolution ,RNA Splicing ,Article ,Evolution, Molecular ,Structural variation ,RC0254 ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Genetic ,genomics ,SYSTEMATIC ANALYSIS ,Genetics ,Genomics--Databases ,Humans ,Genetic Testing ,Molecular Biology ,SIGNATURES ,Whole genome sequencing ,1000 Multidisciplinary ,Chromothripsis ,Science & Technology ,RC0254 Neoplasms. Tumors. Oncology (including Cancer) ,Information Dissemination ,ResearchInstitutes_Networks_Beacons/mcrc ,Prevention ,Biology and Life Sciences ,Molecular ,Oncogenes ,Cloud Computing ,medicine.disease ,Genòmica ,Compute clouds ,Mutation ,570 Life sciences ,biology ,COMPREHENSIVE CHARACTERIZATION ,Genètica ,Whole Genome Sequencing--methods ,Background information ,Genetic / genetics ,Genome ,Germ-Line Mutation / genetics ,Human / genetics ,ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium ,Medizin ,Whole-genome ,Genome mapping ,Neoplasms ,2.1 Biological and endogenous factors ,Promoter Regions, Genetic ,Càncer -- Aspectes genètics ,Telomerase ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,Multidisciplinary ,Manchester Cancer Research Centre ,genomics, cancer, profiling ,3rd-DAS ,10124 Institute of Molecular Life Sciences ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Multidisciplinary Sciences ,Parallel sequencing ,Female ,profiling ,Medical Genetics ,Engineering sciences. Technology ,Biotechnology ,General Science & Technology ,The Cancer Genome Atlas ,610 Medicine & health ,Computational biology ,QH426 Genetics ,Biology ,Consortium of the International Cancer Genome Consortium ,Promoter Regions ,Germline mutation ,Pan-cancer analysis ,Krabbameinsrannsóknir ,medicine ,cancer ,ddc:610 ,QH426 ,Germ-Line Mutation ,Medicinsk genetik ,Krabbamein ,030304 developmental biology ,Cell Proliferation ,LANDSCAPE ,Genome, Human ,comprehensive characterization ,Pan-cancer analysis of whole genomes ,Point mutation ,Human Genome ,Reproducibility of Results ,SOMATIC MUTATIONS ,EVOLUTION ,Cancer, sequencing, Chromothripsis, telomere ,DNA-DAMAGE ,Mutagenesis ,PATTERNS ,3111 Biomedicine ,CHARACTERIZATION - Abstract
Publisher's version (útgefin grein), Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18., Competing interests Gad Getz receives research funds from IBM and Pharmacyclics and is an inventor on patent applications related to MuTect, ABSOLUTE, MutSig, MSMuTect, MSMutSig and POLYSOLVER. Hikmat Al-Ahmadie is consultant for AstraZeneca and Bristol-Myers Squibb. Samuel Aparicio is a founder and shareholder of Contextual Genomics. Pratiti Bandopadhayay receives grant funding from Novartis for an unrelated project. Rameen Beroukhim owns equity in Ampressa Therapeutics. Andrew Biankin receives grant funding from Celgene, AstraZeneca and is a consultant for or on advisory boards of AstraZeneca, Celgene, Elstar Therapeutics, Clovis Oncology and Roche. Ewan Birney is a consultant for Oxford Nanopore, Dovetail and GSK. Marcus Bosenberg is a consultant for Eli Lilly. Atul Butte is a cofounder of and consultant for Personalis, NuMedii, a consultant for Samsung, Geisinger Health, Mango Tree Corporation, Regenstrief Institute and in the recent past a consultant for 10x Genomics and Helix, a shareholder in Personalis, a minor shareholder in Apple, Twitter, Facebook, Google, Microsoft, Sarepta, 10x Genomics, Amazon, Biogen, CVS, Illumina, Snap and Sutro and has received honoraria and travel reimbursement for invited talks from Genentech, Roche, Pfizer, Optum, AbbVie and many academic institutions and health systems. Carlos Caldas has served on the Scientific Advisory Board of Illumina. Lorraine Chantrill acted on an advisory board for AMGEN Australia in the past 2 years. Andrew D. Cherniack receives research funding from Bayer. Helen Davies is an inventor on a number of patent applications that encompass the use of mutational signatures. Francisco De La Vega was employed at Annai Systems during part of the project. Ronny Drapkin serves on the scientific advisory board of Repare Therapeutics and Siamab Therapeutics. Rosalind Eeles has received an honorarium for the GU-ASCO meeting in San Francisco in January 2016 as a speaker, a honorarium and support from Janssen for the RMH FR meeting in November 2017 as a speaker (title: genetics and prostate cancer), a honorarium for an University of Chicago invited talk in May 2018 as speaker and an educational honorarium paid by Bayer & Ipsen to attend GU Connect ‘Treatment sequencing for mCRPC patients within the changing landscape of mHSPC’ at a venue at ESMO, Barcelona, on 28 September 2019. Paul Flicek is a member of the scientific advisory boards of Fabric Genomics and Eagle Genomics. Ronald Ghossein is a consultant for Veracyte. Dominik Glodzik is an inventor on a number of patent applications that encompass the use of mutational signatures. Eoghan Harrington is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Yann Joly is responsible for the Data Access Compliance Office (DACO) of ICGC 2009-2018. Sissel Juul is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Vincent Khoo has received personal fees and non-financial support from Accuray, Astellas, Bayer, Boston Scientific and Janssen. Stian Knappskog is a coprincipal investigator on a clinical trial that receives research funding from AstraZeneca and Pfizer. Ignaty Leshchiner is a consultant for PACT Pharma. Carlos López-Otín has ownership interest (including stock and patents) in DREAMgenics. Matthew Meyerson is a scientific advisory board chair of, and consultant for, OrigiMed, has obtained research funding from Bayer and Ono Pharma and receives patent royalties from LabCorp. Serena Nik-Zainal is an inventor on a number of patent applications that encompass the use of mutational signatures. Nathan Pennell has done consulting work with Merck, Astrazeneca, Eli Lilly and Bristol-Myers Squibb. Xose S. Puente has ownership interest (including stock and patents in DREAMgenics. Benjamin J. Raphael is a consultant for and has ownership interest (including stock and patents) in Medley Genomics. Jorge Reis-Filho is a consultant for Goldman Sachs and REPARE Therapeutics, member of the scientific advisory board of Volition RX and Paige.AI and an ad hoc member of the scientific advisory board of Ventana Medical Systems, Roche Tissue Diagnostics, InVicro, Roche, Genentech and Novartis. Lewis R. Roberts has received grant support from ARIAD Pharmaceuticals, Bayer, BTG International, Exact Sciences, Gilead Sciences, Glycotest, RedHill Biopharma, Target PharmaSolutions and Wako Diagnostics and has provided advisory services to Bayer, Exact Sciences, Gilead Sciences, GRAIL, QED Therapeutics and TAVEC Pharmaceuticals. Richard A. Scolyer has received fees for professional services from Merck Sharp & Dohme, GlaxoSmithKline Australia, Bristol-Myers Squibb, Dermpedia, Novartis Pharmaceuticals Australia, Myriad, NeraCare GmbH and Amgen. Tal Shmaya is employed at Annai Systems. Reiner Siebert has received speaker honoraria from Roche and AstraZeneca. Sabina Signoretti is a consultant for Bristol-Myers Squibb, AstraZeneca, Merck, AACR and NCI and has received funding from Bristol-Myers Squibb, AstraZeneca, Exelixis and royalties from Biogenex. Jared Simpson has received research funding and travel support from Oxford Nanopore Technologies. Anil K. Sood is a consultant for Merck and Kiyatec, has received research funding from M-Trap and is a shareholder in BioPath. Simon Tavaré is on the scientific advisory board of Ipsen and a consultant for Kallyope. John F. Thompson has received honoraria and travel support for attending advisory board meetings of GlaxoSmithKline and Provectus and has received honoraria for participation in advisory boards for MSD Australia and BMS Australia. Daniel Turner is a full-time employee of Oxford Nanopore Technologies and is a stock holder. Naveen Vasudev has received speaker honoraria and/or consultancy fees from Bristol-Myers Squibb, Pfizer, EUSA pharma, MSD and Novartis. Jeremiah A. Wala is a consultant for Nference. Daniel J. Weisenberger is a consultant for Zymo Research. Dai-Ying Wu is employed at Annai Systems. Cheng-Zhong Zhang is a cofounder and equity holder of Pillar Biosciences, a for-profit company that specializes in the development of targeted sequencing assays. The other authors declare no competing interests.
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- 2020
16. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
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Bailey, Matthew H, Meyerson, William U, Dursi, Lewis Jonathan, Wang, Liang-Bo, Dong, Guanlan, Liang, Wen-Wei, Weerasinghe, Amila, Shantao, Li, Kelso, Sean, Saksena, Gordon, Ellrott, Kyle, Wendl, Michael C, Wheeler, David A, Getz, Gad, Simpson, Jared T, Gerstein, Mark B, Ding, Lirehan, Akbani, Pavana, Anur, Matthew, H Bailey, Alex, Buchanan, Kami, Chiotti, Kyle, Covington, Allison, Creason, Ding, Li, Kyle, Ellrott, Fan, Yu, Steven, Foltz, Gad, Getz, Walker, Hale, David, Haussler, Julian, M Hess, Carolyn, M Hutter, Cyriac, Kandoth, Katayoon, Kasaian, Melpomeni, Kasapi, Dave, Larson, Ignaty, Leshchiner, John, Letaw, Singer, Ma, Michael, D McLellan, Yifei, Men, Gordon, B Mills, Beifang, Niu, Myron, Peto, Amie, Radenbaugh, Sheila, M Reynolds, Gordon, Saksena, Heidi, Sofia, Chip, Stewart, Adam, J Struck, Joshua, M Stuart, Wenyi, Wang, John, N Weinstein, David, A Wheeler, Christopher, K Wong, Liu, Xi, Kai, Ye, Matthias, Bieg, Paul, C Boutros, Ivo, Buchhalter, Adam, P Butler, Ken, Chen, Zechen, Chong, Oliver, Drechsel, Lewis Jonathan Dursi, Roland, Eils, Shadrielle M, G Espiritu, Robert, S Fulton, Shengjie, Gao, Josep L, L Gelpi, Mark, B Gerstein, Santiago, Gonzalez, Ivo, G Gut, Faraz, Hach, Michael, C Heinold, Jonathan, Hinton, Taobo, Hu, Vincent, Huang, Huang, Yi, Barbara, Hutter, David, R Jones, Jongsun, Jung, Natalie, Jäger, Hyung-Lae, Kim, Kortine, Kleinheinz, Sushant, Kumar, Yogesh, Kumar, Christopher, M Lalansingh, Ivica, Letunic, Dimitri, Livitz, Eric, Z Ma, Yosef, E Maruvka, R Jay Mashl, Andrew, Menzies, Ana, Milovanovic, Morten Muhlig Nielsen, Stephan, Ossowski, Nagarajan, Paramasivam, Jakob Skou Pedersen, Marc, D Perry, Montserrat, Puiggròs, Keiran, M Raine, Esther, Rheinbay, Romina, Royo, S Cenk Sahinalp, Iman, Sarrafi, Matthias, Schlesner, Jared, T Simpson, Lucy, Stebbings, Miranda, D Stobbe, Jon, W Teague, Grace, Tiao, David, Torrents, Jeremiah, A Wala, Jiayin, Wang, Sebastian, M Waszak, Joachim, Weischenfeldt, Michael, C Wendl, Johannes, Werner, 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Rosamonde, E Banks, Stefano, Barbi, Andrew, P Barbour, Jonathan, Barenboim, Jill, Barnholtz-Sloan, Hugh, Barr, Elisabet, Barrera, John, Bartlett, Javier, Bartolome, Bassi, Claudio, Oliver, F Bathe, Daniel, Baumhoer, Prashant, Bavi, Stephen, B Baylin, Wojciech, Bazant, Duncan, Beardsmore, Timothy, A Beck, Sam, Behjati, Andreas, Behren, Cindy, Bell, Sergi, Beltran, Christopher, Benz, Andrew, Berchuck, Anke, K Bergmann, Erik, N Bergstrom, Benjamin, P Berman, Daniel, M Berney, Stephan, H Bernhart, Rameen, Beroukhim, Mario, Berrios, Samantha, Bersani, Johanna, Bertl, Miguel, Betancourt, Vinayak, Bhandari, Shriram, G Bhosle, Andrew, V Biankin, Darell, Bigner, Hans, Binder, Ewan, Birney, Michael, Birrer, Nidhan, K Biswas, Bodil, Bjerkehagen, Tom, Bodenheimer, Lori, Boice, Giada, Bonizzato, Johann, S De Bono, Arnoud, Boot, Moiz, S Bootwalla, Ake, Borg, Arndt, Borkhardt, Keith, A Boroevich, Ivan, Borozan, Christoph, Borst, Marcus, Bosenberg, Mattia, Bosio, Jacqueline, Boultwood, Guillaume, 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G, Aukema, S, Auman, J, Aure, M, Awadalla, P, Aymerich, M, Bader, G, Baez-Ortega, A, Bailey, P, Balasundaram, M, Balu, S, Bandopadhayay, P, Banks, R, Barbi, S, Barbour, A, Barenboim, J, Barnholtz-Sloan, J, Barr, H, Barrera, E, Bartlett, J, Bartolome, J, Bassi, C, Bathe, O, Baumhoer, D, Bavi, P, Baylin, S, Bazant, W, Beardsmore, D, Beck, T, Behjati, S, Behren, A, Bell, C, Beltran, S, Benz, C, Berchuck, A, Bergmann, A, Bergstrom, E, Berman, B, Berney, D, Bernhart, S, Beroukhim, R, Berrios, M, Bersani, S, Bertl, J, Betancourt, M, Bhandari, V, Bhosle, S, Biankin, A, Bigner, D, Binder, H, Birney, E, Birrer, M, Biswas, N, Bjerkehagen, B, Bodenheimer, T, Boice, L, Bonizzato, G, De Bono, J, Boot, A, Bootwalla, M, Borg, A, Borkhardt, A, Boroevich, K, Borozan, I, Borst, C, Bosenberg, M, Bosio, M, Boultwood, J, Bourque, G, Bova, G, Bowen, D, Bowlby, R, Bowtell, D, Boyault, S, Boyce, R, Boyd, J, Brazma, A, Brennan, P, Brewer, D, Brinkman, A, Bristow, R, Broaddus, R, Brock, J, Brock, M, Broeks, A, Brooks, A, Brooks, D, Brors, B, Brunak, S, Bruxner, T, Bruzos, A, Buchholz, C, Bullman, S, Burke, H, Burkhardt, B, Burns, K, Busanovich, J, Bustamante, C, Butte, A, Byrne, N, Borresen-Dale, A, Caesar-Johnson, S, Cafferkey, A, Cahill, D, Calabrese, C, Caldas, C, Calvo, F, Camacho, N, Campbell, P, Campo, E, Cantu, C, Cao, S, Carey, T, Carlevaro-Fita, J, Carlsen, R, Cataldo, I, Cazzola, M, Cebon, J, Cerfolio, R, Chadwick, D, Chakravarty, D, Chalmers, D, Chan, C, Chan, K, Chan-Seng-Yue, M, Chandan, V, Chang, D, Chanock, S, Chantrill, L, Chateigner, A, Chatterjee, N, Chayama, K, Chen, H, Chen, J, Chen, Y, Chen, Z, Cherniack, A, Chien, J, Chiew, Y, Chin, S, Cho, J, Cho, S, Choi, J, Choi, W, Chomienne, C, Choo, S, Chou, A, Christ, A, Christie, E, Chuah, E, Cibulskis, C, Cibulskis, K, Cingarlini, S, Clapham, P, Claviez, A, Cleary, S, Cloonan, N, Cmero, M, Collins, C, Connor, A, Cooke, S, Cooper, C, Cope, L, Corbo, V, Cordes, M, Cordner, S, Cortes-Ciriano, I, Cowin, P, Craft, B, Craft, D, Creighton, C, Cun, Y, Curley, E, Cutcutache, I, Czajka, K, Czerniak, B, Dagg, R, Danilova, L, Davi, M, Davidson, N, Davies, H, Davis, I, Davis-Dusenbery, B, Dawson, K, De La Vega, F, De Paoli-Iseppi, R, Defreitas, T, Dei Tos, A, Delaneau, O, Demchok, J, Demeulemeester, J, Demidov, G, Demircioglu, D, Dennis, N, Denroche, R, Dentro, S, Desai, N, Deshpande, V, Deshwar, A, Desmedt, C, Deu-Pons, J, Dhalla, N, Dhani, N, Dhingra, P, Dhir, R, Dibiase, A, Diamanti, K, Ding, S, Dinh, H, Dirix, L, Doddapaneni, H, Donmez, N, Dow, M, Drapkin, R, Drews, R, Serge, S, Dudderidge, T, Dueso-Barroso, A, Dunford, A, Dunn, M, Duthie, F, Dutton-Regester, K, Eagles, J, Easton, D, Edmonds, S, Edwards, P, Edwards, S, Eeles, R, Ehinger, A, Eils, J, El-Naggar, A, Eldridge, M, Erkek, S, Escaramis, G, Estivill, X, Etemadmoghadam, D, Eyfjord, J, Faltas, B, Fan, D, Faquin, W, Farcas, C, Fassan, M, Fatima, A, Favero, F, Fayzullaev, N, Felau, I, Fereday, S, Ferguson, M, Ferretti, V, Feuerbach, L, Field, M, Fink, J, Finocchiaro, G, Fisher, C, Fittall, M, Fitzgerald, A, Fitzgerald, R, Flanagan, A, Fleshner, N, Flicek, P, Foekens, J, Fong, K, Fonseca, N, Foster, C, Fox, N, Fraser, M, Frazer, S, Frenkel-Morgenstern, M, Friedman, W, Frigola, J, Fronick, C, Fujimoto, A, Fujita, M, Fukayama, M, Fulton, L, Furuta, M, Futreal, P, Fullgrabe, A, Gabriel, S, Gallinger, S, Gambacorti Passerini, C, Gao, J, Garraway, L, Garred, O, Garrison, E, Garsed, D, Gehlenborg, N, George, J, Gerhard, D, Gerhauser, C, Gershenwald, J, Gerstung, M, Ghori, M, Ghossein, R, Giama, N, Gibbs, R, Gill, A, Gill, P, Giri, D, Glodzik, D, Gnanapragasam, V, Goebler, M, Goldman, M, Gomez, C, Gonzalez-Perez, A, Gordenin, D, Gossage, J, Gotoh, K, Govindan, R, Grabau, D, Graham, J, Grant, R, Green, A, Green, E, Greger, L, Grehan, N, Grimaldi, S, Grimmond, S, Grossman, R, Grundhoff, A, Gundem, G, Guo, Q, Gupta, M, Gupta, S, Gut, M, Goke, J, Ha, G, Haake, A, Haan, D, Haas, S, Haase, K, Haber, J, Habermann, N, Haider, S, Hama, N, Hamdy, F, Hamilton, A, Hamilton, M, Han, L, Hanna, G, Hansmann, M, Haradhvala, N, Harismendy, O, Harliwong, I, Harmanci, A, Harrington, E, Hasegawa, T, Hawkins, S, Hayami, S, Hayashi, S, Hayes, D, Hayes, S, Hayward, N, Hazell, S, He, Y, Heath, A, Heath, S, Hedley, D, Hegde, A, Heiman, D, Heins, Z, Heisler, L, Hellstrom-Lindberg, E, Helmy, M, Heo, S, Hepperla, A, Heredia-Genestar, J, Herrmann, C, Hersey, P, Hilmarsdottir, H, Hirano, S, Hiraoka, N, Hoadley, K, Hobolth, A, Hodzic, E, Hoell, J, Hoffmann, S, Hofmann, O, Holbrook, A, Holik, A, Hollingsworth, M, Holmes, O, Holt, R, Hong, C, Hong, E, Hong, J, Hooijer, G, Hornshoj, H, Hosoda, F, Hou, Y, Hovestadt, V, Howat, W, Hoyle, A, Hruban, R, Hu, J, Hua, X, Huang, K, Huang, M, Huber, W, Hudson, T, Hummel, M, Hung, J, Huntsman, D, Hupp, T, Huse, J, Huska, M, Hubschmann, D, Iacobuzio-Donahue, C, Imbusch, C, Imielinski, M, Imoto, S, Isaacs, W, Isaev, K, Ishikawa, S, Iskar, M, Islam, S, Ittmann, M, Ivkovic, S, Izarzugaza, J, Jacquemier, J, Jakrot, V, Jamieson, N, Jang, G, Jang, S, Jayaseelan, J, Jayasinghe, R, Jefferys, S, Jegalian, K, Jennings, J, Jeon, S, Jerman, L, Ji, Y, Jiao, W, Johansson, P, Johns, A, Johns, J, Johnson, R, Johnson, T, Jolly, C, Joly, Y, Jonasson, J, Jones, C, Jones, N, Jones, S, Jonkers, J, Ju, Y, Juhl, H, Juul, M, Juul, R, Juul, S, Kabbe, R, Kahles, A, Kahraman, A, Kaiser, V, Kakavand, H, Kalimuthu, S, von Kalle, C, Kang, K, Karaszi, K, Karlan, B, Karlic, R, Karsch, D, Kassahn, K, Katai, H, Kato, M, Katoh, H, Kawakami, Y, Kay, J, Kazakoff, S, Kazanov, M, Keays, M, Kebebew, E, Kefford, R, Kellis, M, Kench, J, Kennedy, C, Kerssemakers, J, Khoo, D, Khoo, V, Khuntikeo, N, Khurana, E, Kilpinen, H, Kim, J, Kim, Y, King, T, Klapper, W, Klimczak, L, Knappskog, S, Kneba, M, Knoppers, B, Koh, Y, Jan, K, Komura, D, Komura, M, Kong, G, Kool, M, Korbel, J, Korchina, V, Korshunov, A, Koscher, M, Koster, R, Kote-Jarai, Z, Koures, A, Kovacevic, M, Kremeyer, B, Kretzmer, H, Kreuz, M, Krishnamurthy, S, Kube, D, Kumar, K, Kumar, P, Kundra, R, Kubler, K, Kuppers, R, Lagergren, J, Lai, P, Laird, P, Lakhani, S, Lalonde, E, Lamaze, F, Lambert, A, Lander, E, Landgraf, P, Landoni, L, Langerod, A, Lanzos, A, Larsimont, D, Larsson, E, Lathrop, M, Lau, L, Lawerenz, C, Lawlor, R, Lawrence, M, Lazar, A, Le, X, Lee, D, Lee, E, Lee, H, Lee, J, Lee, M, Lee-Six, H, Lehmann, K, Lehrach, H, Lenze, D, Leonard, C, Leongamornlert, D, Letourneau, L, Levine, D, Lewis, L, Ley, T, Li, C, Li, H, Li, J, Li, L, Li, X, Li, Y, Liang, H, Liang, S, Lichter, P, Lin, P, Lin, Z, Linehan, W, Lingjaerde, O, Liu, D, Liu, E, Liu, F, Liu, J, Liu, X, Livingstone, J, Livni, N, Lochovsky, L, Loeffler, M, Long, G, Lopez-Guillermo, A, Lou, S, Louis, D, Lovat, L, Lu, Y, Luchini, C, Lungu, I, Luo, X, Luxton, H, Lynch, A, Lype, L, Lopez, C, Lopez-Otin, C, Ma, Y, Macgrogan, G, Macrae, S, Macintyre, G, Madsen, T, Maejima, K, Mafficini, A, Maglinte, D, Maitra, A, Majumder, P, Malcovati, L, Malikic, S, Malleo, G, Mann, G, Mantovani-Loffler, L, Marchal, K, Marchegiani, G, Mardis, E, Margolin, A, Marin, M, Markowetz, F, Markowski, J, Marks, J, Marques-Bonet, T, Marra, M, Marsden, L, Martens, J, Martin, S, Martin-Subero, J, Martincorena, I, Martinez-Fundichely, A, Massie, C, Matthew, T, Matthews, L, Mayer, E, Mayes, S, Mayo, M, Mbabaali, F, Mccune, K, Mcdermott, U, Mcgillivray, P, Mcpherson, J, Mcpherson, T, Meier, S, Meng, A, Meng, S, Merrett, N, Merson, S, Meyerson, M, Mieczkowski, P, Mihaiescu, G, Mijalkovic, S, Mijalkovic-Lazic, A, Mikkelsen, T, Milella, M, Mileshkin, L, Miller, C, Miller, D, Miller, J, Minner, S, Miotto, M, Arnau, G, Mirabello, L, Mitchell, C, Mitchell, T, Miyano, S, Miyoshi, N, Mizuno, S, Molnar-Gabor, F, Moore, M, Moore, R, Morganella, S, Morris, Q, Morrison, C, Mose, L, Moser, C, Muinos, F, Mularoni, L, Mungall, A, Mungall, K, Musgrove, E, Mustonen, V, Mutch, D, Muyas, F, Muzny, D, Munoz, A, Myers, J, Myklebost, O, Moller, P, Nagae, G, Nagrial, A, Nahal-Bose, H, Nakagama, H, Nakagawa, H, Nakamura, H, Nakamura, T, Nakano, K, Nandi, T, Nangalia, J, Nastic, M, Navarro, A, Navarro, F, Neal, D, Nettekoven, G, Newell, F, Newhouse, S, Newton, Y, Ng, A, Nicholson, J, Nicol, D, Nie, Y, Nielsen, G, Nik-Zainal, S, Noble, M, Nones, K, Northcott, P, Notta, F, O'Connor, B, O'Donnell, P, O'Donovan, M, O'Meara, S, O'Neill, B, O'Neill, J, Ocana, D, Ochoa, A, Oesper, L, Ogden, C, Ohdan, H, Ohi, K, Ohno-Machado, L, Oien, K, Ojesina, A, Ojima, H, Okusaka, T, Omberg, L, Ong, C, Ott, G, Ouellette, B, P'Ng, C, Paczkowska, M, Paiella, S, Pairojkul, C, Pajic, M, Pan-Hammarstrom, Q, Papaemmanuil, E, Papatheodorou, I, Park, J, Park, K, Park, P, Parker, J, Parsons, S, Pass, H, Pasternack, D, Pastore, A, Patch, A, Pauporte, I, Pea, A, Pearson, J, Pedamallu, C, Pederzoli, P, Peifer, M, Pennell, N, Perou, C, Petersen, G, Petrelli, N, Petryszak, R, Pfister, S, Phillips, M, Pich, O, Pickett, H, Pihl, T, Pillay, N, Pinder, S, Pinese, M, Pinho, A, Pitkanen, E, Pivot, X, Pineiro-Yanez, E, Planko, L, Plass, C, Polak, P, Pons, T, Popescu, I, Potapova, O, Prasad, A, Preston, S, Prinz, M, Pritchard, A, Prokopec, S, Provenzano, E, Puente, X, Puig, S, Pulido-Tamayo, S, Pupo, G, Purdie, C, Quinn, M, Rabionet, R, Rader, J, Radlwimmer, B, Radovic, P, Raeder, B, Ramakrishna, M, Ramakrishnan, K, Ramalingam, S, Raphael, B, Rathmell, W, Rausch, T, Reifenberger, G, Reimand, J, Reis-Filho, J, Reuter, V, Reyes-Salazar, I, Reyna, M, Riazalhosseini, Y, Richardson, A, Richter, J, Ringel, M, Ringner, M, Rino, Y, Rippe, K, Roach, J, Roberts, L, Roberts, N, Roberts, S, Robertson, A, Rodriguez, J, Rodriguez-Martin, B, Rodriguez-Gonzalez, F, Roehrl, M, Rohde, M, Rokutan, H, Romieu, G, Rooman, I, Roques, T, Rosebrock, D, Rosenberg, M, Rosenstiel, P, Rosenwald, A, Rowe, E, Rozen, S, Rubanova, Y, Rubin, M, Rubio-Perez, C, Rudneva, V, Rusev, B, Ruzzenente, A, Ratsch, G, Sabarinathan, R, Sabelnykova, V, Sadeghi, S, Saini, N, Saito-Adachi, M, Salcedo, A, Salgado, R, Salichos, L, Sallari, R, Saller, C, Salvia, R, Sam, M, Samra, J, Sanchez-Vega, F, Sander, C, Sanders, G, Sarin, R, Sasaki-Oku, A, Sauer, T, Sauter, G, Saw, R, Scardoni, M, Scarlett, C, Scarpa, A, Scelo, G, Schadendorf, D, Schein, J, Schilhabel, M, Schlomm, T, Schmidt, H, Schramm, S, Schreiber, S, Schultz, N, Schumacher, S, Schwarz, R, Scolyer, R, Scott, D, Scully, R, Seethala, R, Segre, A, Selander, I, Semple, C, Senbabaoglu, Y, Sengupta, S, Sereni, E, Serra, S, Sgroi, D, Shackleton, M, Shah, N, Shahabi, S, Shang, C, Shang, P, Shapira, O, Shelton, T, Shen, C, Shen, H, Shepherd, R, Shi, R, Shi, Y, Shiah, Y, Shibata, T, Shih, J, Shimizu, E, Shimizu, K, Shin, S, Shiraishi, Y, Shmaya, T, Shmulevich, I, Shorser, S, Short, C, Shrestha, R, Shringarpure, S, Shriver, C, Shuai, S, Sidiropoulos, N, Siebert, R, Sieuwerts, A, Sieverling, L, Signoretti, S, Sikora, K, Simbolo, M, Simon, R, Simons, J, Simpson, P, Singer, S, Sinnott-Armstrong, N, Sipahimalani, P, Skelly, T, Smid, M, Smith, J, Smith-McCune, K, Socci, N, Soloway, M, Song, L, Sood, A, Sothi, S, Sotiriou, C, Soulette, C, Span, P, Spellman, P, Sperandio, N, Spillane, A, Spiro, O, Spring, J, Staaf, J, Stadler, P, Staib, P, Stark, S, Stefansson, O, Stegle, O, Stein, L, Stenhouse, A, Stilgenbauer, S, Stratton, M, Stretch, J, Stunnenberg, H, Su, H, Su, X, Sun, R, Sungalee, S, Susak, H, Suzuki, A, Sweep, F, Szczepanowski, M, Sultmann, H, Yugawa, T, Tam, A, Tamborero, D, Tan, B, Tan, D, Tan, P, Tanaka, H, Taniguchi, H, Tanskanen, T, Tarabichi, M, Tarnuzzer, R, Tarpey, P, Taschuk, M, Tatsuno, K, Tavare, S, Taylor, D, Taylor-Weiner, A, Teh, B, Tembe, V, Temes, J, Thai, K, Thayer, S, Thiessen, N, Thomas, G, Thomas, S, Thompson, A, Thompson, J, Thompson, R, Thorne, H, Thorne, L, Thorogood, A, Tijanic, N, Timms, L, Tirabosco, R, Tojo, M, Tommasi, S, Toon, C, Toprak, U, Tortora, G, Tost, J, Totoki, Y, Townend, D, Traficante, N, Treilleux, I, Trotta, J, Trumper, L, Tsao, M, Tsunoda, T, Tubio, J, Tucker, O, Turkington, R, Turner, D, Tutt, A, Ueno, M, Ueno, N, Umbricht, C, Umer, H, Underwood, T, Urban, L, Urushidate, T, Ushiku, T, Uuskula-Reimand, L, Valencia, A, Van Den Berg, D, Van Laere, S, Van Loo, P, Van Meir, E, Van den Eynden, G, Van der Kwast, T, Vasudev, N, Vazquez, M, Vedururu, R, Veluvolu, U, Vembu, S, Verbeke, L, Vermeulen, P, Verrill, C, Viari, A, Vicente, D, Vicentini, C, Raghavan, K, Viksna, J, Vilain, R, Villasante, I, Vincent-Salomon, A, Visakorpi, T, Voet, D, Vyas, P, Vazquez-Garcia, I, Waddell, N, Wadelius, C, Wadi, L, Wagener, R, Wang, Q, Wang, Y, Wang, Z, Waring, P, Warnatz, H, Warrell, J, Warren, A, Wedge, D, Weichenhan, D, Weinberger, P, Weisenberger, D, Welch, I, Whalley, J, Whitaker, H, Wigle, D, Wilkerson, M, Williams, A, Wilmott, J, Wilson, G, Wilson, J, Wilson, R, Winterhoff, B, Wintersinger, J, Wiznerowicz, M, Wolf, S, Wong, B, Wong, T, Wong, W, Woo, Y, Wood, S, Wouters, B, Wright, A, Wright, D, Wright, M, Wu, C, Wu, D, Wu, G, Wu, J, Wu, K, Wu, Y, Xia, T, Xiang, Q, Xiao, X, Xing, R, Xiong, H, Xu, Q, Xu, Y, Yachida, S, Yamaguchi, R, Yamamoto, M, Yamamoto, S, Yamaue, H, Yang, F, Yang, H, Yang, J, Yang, L, Yang, S, Yang, T, Yang, Y, Yao, X, Yaspo, M, Yates, L, Yau, C, Ye, C, Yoon, C, Yoon, S, Yousif, F, Yu, J, Yu, K, Yu, W, Yu, Y, Yuan, K, Yuan, Y, Yuen, D, Zaikova, O, Zamora, J, Zapatka, M, Zenklusen, J, Zenz, T, Zeps, N, Zhang, C, Zhang, F, Zhang, H, Zhang, X, Zhang, Y, Zhang, Z, Zhao, Z, Zheng, L, Zheng, X, Zhou, W, Zhou, Y, Bin, Z, Zhu, H, Zhu, J, Zhu, S, Zou, L, Zou, X, Defazio, A, van As, N, van Deurzen, C, van de Vijver, M, van't Veer, L, von Mering, C, Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Tampere University, BioMediTech, TAYS Cancer Centre, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, University of St Andrews. Statistics, University of St Andrews. School of Medicine, University of Zurich, Gerstein, Mark B, Ding, Li, Bailey, Matthew H [0000-0003-4526-9727], Wheeler, David A [0000-0002-9056-6299], Gerstein, Mark B [0000-0002-9746-3719], Faculty of Economic and Social Sciences and Solvay Business School, Lauri Antti Aaltonen / Principal Investigator, Genome-Scale Biology (GSB) Research Program, Department of Medical and Clinical Genetics, Organismal and Evolutionary Biology Research Programme, Helsinki Institute for Information Technology, Institute of Biotechnology, Bioinformatics, Department of Computer Science, Faculty of Medicine, and HUS Helsinki and Uusimaa Hospital District
- Subjects
VARIANTS ,0302 clinical medicine ,706/648/697/129/2043 ,Databases, Genetic ,Cancer genomics ,SOMATIC POINT MUTATIONS ,Càncer ,lcsh:Science ,Exome ,Exome sequencing ,Cancer ,Base Composition ,Neoplasms -- genetics ,1184 Genetics, developmental biology, physiology ,3100 General Physics and Astronomy ,3. Good health ,030220 oncology & carcinogenesis ,Science & Technology - Other Topics ,Transformació genètica ,Genetic databases ,Erfðarannsóknir ,Human ,GENES ,Science ,1600 General Chemistry ,General Biochemistry, Genetics and Molecular Biology ,RC0254 ,03 medical and health sciences ,Genetic ,SDG 3 - Good Health and Well-being ,1300 General Biochemistry, Genetics and Molecular Biology ,Exome Sequencing ,Genetics ,Humans ,Author Correction ,Retrospective Studies ,Whole genome sequencing ,Comparative genomics ,Science & Technology ,RC0254 Neoplasms. Tumors. Oncology (including Cancer) ,INSERTIONS ,DNA ,PERFORMANCE ,Human genetics ,Communication and replication ,Cancérologie ,692/4028/67/69 ,Genòmica ,030104 developmental biology ,Mutation ,Genome mutation ,Human genome ,lcsh:Q ,COMPREHENSIVE CHARACTERIZATION ,Genètica ,0301 basic medicine ,Medizin ,General Physics and Astronomy ,Genome ,Whole Exome Sequencing ,Genetic transformation ,International Cancer Genome Consortium ,Neoplasms ,631/114/2399 ,Genamengi ,Medicine and Health Sciences ,Medicine(all) ,Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] ,Multidisciplinary ,318 Medical biotechnology ,Exome -- genetics ,article ,Exons ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Multidisciplinary Sciences ,CAPTURE ,1181 Ecology, evolutionary biology ,oncology ,DNA, Intergenic ,139 ,Medical Genetics ,Biotechnology ,ICGC/TCGA Pan-Cancer Analysis ,3122 Cancers ,610 Medicine & health ,45/23 ,QH426 Genetics ,Biology ,MC3 Working Group ,Databases ,Germline mutation ,PCAWG novel somatic mutation calling methods working group ,Krabbameinsrannsóknir ,Cancer Genome Atlas ,Genome, Human -- genetics ,ddc:610 ,QH426 ,Medicinsk genetik ,Krabbamein ,Intergenic ,Whole Genome Sequencing ,Genome, Human ,Human Genome ,PCAWG Consortium ,DAS ,General Chemistry ,DELETIONS ,Good Health and Well Being ,10032 Clinic for Oncology and Hematology ,3111 Biomedicine ,631/1647/2217/748 - Abstract
MC3 Working Group: Rehan Akbani21, Pavana Anur22, Matthew H. Bailey1,2,3, Alex Buchanan9, Kami Chiotti9, Kyle Covington12,23, Allison Creason9, Li Ding1,2,3,20, Kyle Ellrott9, Yu Fan21, Steven Foltz1,2, Gad Getz8,14,15,16, Walker Hale12, David Haussler24,25, Julian M. Hess8,26, Carolyn M. Hutter27, Cyriac Kandoth28, Katayoon Kasaian29,30, Melpomeni Kasapi27, Dave Larson1 , Ignaty Leshchiner8, John Letaw31, Singer Ma32, Michael D. McLellan1,3,20, Yifei Men32, Gordon B. Mills33,34, Beifang Niu35, Myron Peto22, Amie Radenbaugh24, Sheila M. Reynolds36, Gordon Saksena8, Heidi Sofia27, Chip Stewart8, Adam J. Struck31, Joshua M. Stuart24,37, Wenyi Wang21, John N. Weinstein38, David A. Wheeler12,13, Christopher K. Wong24,39, Liu Xi12 & Kai Ye40,41 21Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 22Molecular and Medical Genetics, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. 23Castle Biosciences Inc, Friendswood, TX 77546, USA. 24UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 25Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 26Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02114, USA. 27National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20894, USA. 28Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. 29Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada. 30Canada’s Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4S6, Canada. 31Computational Biology Program, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA. 32DNAnexus Inc, Mountain View, CA 94040, USA. 33Department of Systems Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA. 34Precision Oncology, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. 35Computer Network Information Center, Chinese Academy of Sciences, Beijing, China. 36Institute for Systems Biology, Seattle, WA 98109, USA. 37Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 38Department of Bioinformatics and Computational Biology and Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 39Biomolecular Engineering Department, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 40School of Elect, PCAWG novel somatic mutation calling methods working group: Matthew H. Bailey1,2,3, Beifang Niu35, Matthias Bieg42,43, Paul C. Boutros6,44,45,46, Ivo Buchhalter43,47,48, Adam P. Butler49, Ken Chen50, Zechen Chong51, Li Ding1,2,3,20, Oliver Drechsel52,53, Lewis Jonathan Dursi6,7, Roland Eils47,48,54,55, Kyle Ellrott9, Shadrielle M. G. Espiritu6, Yu Fan21, Robert S. Fulton1,3,20, Shengjie Gao56, Josep L. l. Gelpi57,58, Mark B. Gerstein5,18,19, Gad Getz8,14,15,16, Santiago Gonzalez59,60, Ivo G. Gut52,61, Faraz Hach62,63, Michael C. Heinold47,48, Julian M. Hess8,26, Jonathan Hinton49, Taobo Hu64, Vincent Huang6, Yi Huang65,66, Barbara Hutter43,67,68, David R. Jones49, Jongsun Jung69, Natalie Jäger47, Hyung-Lae Kim70, Kortine Kleinheinz47,48, Sushant Kumar5,19, Yogesh Kumar64, Christopher M. Lalansingh6, Ignaty Leshchiner8, Ivica Letunic71, Dimitri Livitz8, Eric Z. Ma64, Yosef E. Maruvka8,26,72, R. Jay Mashl1,2, Michael D. McLellan1,3,20, Andrew Menzies49, Ana Milovanovic57, Morten Muhlig Nielsen73, Stephan Ossowski52,53,74, Nagarajan Paramasivam43,47, Jakob Skou Pedersen73,75, Marc D. Perry76,77, Montserrat Puiggròs57, Keiran M. Raine49, Esther Rheinbay8,14,72, Romina Royo57, S. Cenk Sahinalp62,78,79, Gordon Saksena8, Iman Sarrafi62,78, Matthias Schlesner47,80, Jared T. Simpson6,17, Lucy Stebbings49, Chip Stewart8, Miranda D. Stobbe52,61, Jon W. Teague49, Grace Tiao8, David Torrents57,81, Jeremiah A. Wala8,14,82, Jiayin Wang1,40,66, Wenyi Wang21, Sebastian M. Waszak60, Joachim Weischenfeldt60,83,84, Michael C. Wendl1,10,11, Johannes Werner47,85, Zhenggang Wu64, Hong Xue64, Sergei Yakneen60, Takafumi N. Yamaguchi6, Kai Ye40,41, Venkata D. Yellapantula20,86, Christina K. Yung76 & Junjun Zhang76, PCAWG Consortium: Lauri A. Aaltonen87, Federico Abascal49, Adam Abeshouse88, Hiroyuki Aburatani89, David J. Adams49, Nishant Agrawal90, Keun Soo Ahn91, Sung-Min Ahn92, Hiroshi Aikata93, Rehan Akbani21, Kadir C. Akdemir50, Hikmat Al-Ahmadie88, Sultan T. Al-Sedairy94, Fatima Al-Shahrour95, Malik Alawi96,97, Monique Albert98, Kenneth Aldape99,100, Ludmil B. Alexandrov49,101,102, Adrian Ally30, Kathryn Alsop103, Eva G. Alvarez104,105,106, Fernanda Amary107, Samirkumar B. Amin108,109,110, Brice Aminou76, Ole Ammerpohl111,112, Matthew J. Anderson113, Yeng Ang114, Davide Antonello115, Pavana Anur22, Samuel Aparicio116, Elizabeth L. Appelbaum1,117, Yasuhito Arai118, Axel Aretz119, Koji Arihiro93, Shun-ichi Ariizumi120, Joshua Armenia121, Laurent Arnould122, Sylvia Asa123,124, Yassen Assenov125, Gurnit Atwal6,126,127, Sietse Aukema112,128, J. Todd Auman129, Miriam R. Aure130, Philip Awadalla6,126, Marta Aymerich131, Gary D. Bader126, Adrian Baez-Ortega132, Matthew H. Bailey1,2,3, Peter J. Bailey133, Miruna Balasundaram30, Saianand Balu134, Pratiti Bandopadhayay8,135,136, Rosamonde E. Banks137, Stefano Barbi138, Andrew P. Barbour139,140, Jonathan Barenboim6, Jill Barnholtz-Sloan141,142, Hugh Barr143, Elisabet Barrera59, John Bartlett98,144, Javier Bartolome57, Claudio Bassi115, Oliver F. Bathe145,146, Daniel Baumhoer147, Prashant Bavi148, Stephen B. Baylin149,150, Wojciech Bazant59, Duncan Beardsmore151, Timothy A. Beck152,153, Sam Behjati49, Andreas Behren154, Beifang Niu35, Cindy Bell155, Sergi Beltran52,61, Christopher Benz156, Andrew Berchuck157, Anke K. Bergmann158, Erik N. Bergstrom101,102, Benjamin P. Berman159,160,161, Daniel M. Berney162, Stephan H. Bernhart163,164,165, Rameen Beroukhim8,14,82, Mario Berrios166, Samantha Bersani167, Johanna Bertl73,168, Miguel Betancourt169, Vinayak Bhandari6,44, Shriram G. Bhosle49, Andrew V. Biankin133,170,171,172, Matthias Bieg42,43, Darell Bigner173, Hans Binder163,164, Ewan Birney59, Michael Birrer72, Nidhan K. Biswas174, Bodil Bjerkehagen147,175, Tom Bodenheimer134, Lori Boice176, Giada Bonizzato177, Johann S. De Bono178, Arnoud Boot179,180, Moiz S. Bootwalla166, Ake Borg181, Arndt Borkhardt182, Keith A. Boroevich183,184, Ivan Borozan6, Christoph Borst185, Marcus Bosenberg186, Mattia Bosio52,53,57, Jacqueline Boultwood187, Guillaume Bourque188,189, Paul C. Boutros6,44,45,46, G. Steven Bova190, David T. Bowen49,191, Reanne Bowlby30, David D. L. Bowtell103, Sandrine Boyault192, Rich Boyce59, Jeffrey Boyd193, Alvis Brazma59, Paul Brennan194, Daniel S. Brewer195,196, Arie B. Brinkman197, Robert G. Bristow44,198,199,200,201, Russell R. Broaddus99, Jane E. Brock202, Malcolm Brock203, Annegien Broeks204, Angela N. Brooks8,24,37,82, Denise Brooks30, Benedikt Brors67,205,206, Søren Brunak207,208, Timothy J. C. Bruxner113,209, Alicia L. Bruzos104,105,106, Alex Buchanan9, Ivo Buchhalter43,47,48, Christiane Buchholz210, Susan Bullman8,82, Hazel Burke211, Birgit Burkhardt212, Kathleen H. Burns213,214, John Busanovich8,215, Carlos D. Bustamante216,217, Adam P. Butler49, Atul J. Butte218, Niall J. Byrne76, Anne-Lise Børresen-Dale130,219, Samantha J. Caesar-Johnson220, Andy Cafferkey59, Declan Cahill221, Claudia Calabrese59,60, Carlos Caldas222,223, Fabien Calvo224, Niedzica Camacho178, Peter J. Campbell49,225, Elias Campo226,227, Cinzia Cantù177, Shaolong Cao21, Thomas E. Carey228, Joana Carlevaro-Fita229,230,231, Rebecca Carlsen30, Ivana Cataldo167,177, Mario Cazzola232, Jonathan Cebon154, Robert Cerfolio233, Dianne E. Chadwick234, Dimple Chakravarty235, Don Chalmers236, Calvin Wing Yiu Chan47,237, Kin Chan238, Michelle Chan-Seng-Yue148, Vishal S. Chandan239, David K. Chang133,170, Stephen J. Chanock240, Lorraine A. Chantrill170,241, Aurélien Chateigner76,242, Nilanjan Chatterjee149,243, Kazuaki Chayama93, Hsiao-Wei Chen114,121, Jieming Chen218, Ken Chen50, Yiwen Chen21, Zhaohong Chen244, Andrew D. Cherniack8,82, Jeremy Chien245, Yoke-Eng Chiew246,247, Suet-Feung Chin222,223, Juok Cho8, Sunghoon Cho248, Jung Kyoon Choi249, Wan Choi250, Christine Chomienne251, Zechen Chong51, Su Pin Choo252, Angela Chou170,246, Angelika N. Christ113, Elizabeth L. Christie103, Eric Chuah30, Carrie Cibulskis8, Kristian Cibulskis8, Sara Cingarlini253, Peter Clapham49, Alexander Claviez254, Sean Cleary148,255, Nicole Cloonan256, Marek Cmero257,258,259, Colin C. Collins62, Ashton A. Connor255,260, Susanna L. Cooke133, Colin S. Cooper178,196,261, Leslie Cope149, Vincenzo Corbo138,177, Matthew G. Cordes1,262, Stephen M. Cordner263, Isidro Cortés-Ciriano264,265,266, Kyle Covington12,23, Prue A. Cowin267, Brian Craft24, David Craft8,268, Chad J. Creighton269, Yupeng Cun270, Erin Curley271, Ioana Cutcutache179,180, Karolina Czajka272, Bogdan Czerniak99,273, Rebecca A. Dagg274, Ludmila Danilova149, Maria Vittoria Davi275, Natalie R. Davidson276,277,278,279,280, Helen Davies49,281,282, Ian J. Davis283, Brandi N. Davis-Dusenbery284, Kevin J. Dawson49, Francisco M. De La Vega216,217,285, Ricardo De Paoli-Iseppi211, Timothy Defreitas8, Angelo P. Dei Tos286, Olivier Delaneau287,288,289, John A. Demchok220, Jonas Demeulemeester290,291, German M. Demidov52,53,74, Deniz Demircioğlu292,293, Nening M. Dennis221, Robert E. Denroche148, Stefan C. Dentro49,290,294, Nikita Desai76, Vikram Deshpande72, Amit G. Deshwar295, Christine Desmedt296,297, Jordi Deu-Pons298,299, Noreen Dhalla30, Neesha C. Dhani300, Priyanka Dhingra301,302, Rajiv Dhir303, Anthony DiBiase304, Klev Diamanti305, Li Ding1,2,3,20, Shuai Ding306, Huy Q. Dinh159, Luc Dirix307, HarshaVardhan Doddapaneni12, Nilgun Donmez62,78, Michelle T. Dow244, Ronny Drapkin308, Oliver Drechsel52,53, Ruben M. Drews223, Serge Serge49, Tim Dudderidge150,221, Ana Dueso-Barroso57, Andrew J. Dunford8, Michael Dunn309, Lewis Jonathan Dursi6,7, Fraser R. Duthie133,310, Ken Dutton-Regester311, Jenna Eagles272, Douglas F. Easton312,313, Stuart Edmonds314, Paul A. Edwards223,315, Sandra E. Edwards178, Rosalind A. Eeles178,221, Anna Ehinger316, Juergen Eils54,55, Roland Eils47,48,54,55, Adel El-Naggar99,273, Matthew Eldridge223, Kyle Ellrott9, Serap Erkek60, Georgia Escaramis53,317,318, Shadrielle M. G. Espiritu6, Xavier Estivill53,319, Dariush Etemadmoghadam103, Jorunn E. Eyfjord320, Bishoy M. Faltas280, Daiming Fan321, Yu Fan21, William C. Faquin72, Claudiu Farcas244, Matteo Fassan322, Aquila Fatima323, Francesco Favero324, Nodirjon Fayzullaev76, Ina Felau220, Sian Fereday103, Martin L. Ferguson325, Vincent Ferretti76,326, Lars Feuerbach205, Matthew A. Field327, J. Lynn Fink57,113, Gaetano Finocchiaro328, Cyril Fisher221, Matthew W. Fittall290, Anna Fitzgerald329, Rebecca C. Fitzgerald282, Adrienne M. Flanagan330, Neil E. Fleshner331, Paul Flicek59, John A. Foekens332, Kwun M. Fong333, Nuno A. Fonseca59,334, Christopher S. Foster335,336, Natalie S. Fox6, Michael Fraser6, Scott Frazer8, Milana Frenkel-Morgenstern337, William Friedman338, Joan Frigola298, Catrina C. Fronick1,262, Akihiro Fujimoto184, Masashi Fujita184, Masashi Fukayama339, Lucinda A. Fulton1 , Robert S. Fulton1,3,20, Mayuko Furuta184, P. Andrew Futreal340, Anja Füllgrabe59, Stacey B. Gabriel8, Steven Gallinger148,255,260, Carlo Gambacorti-Passerini341, Jianjiong Gao121, Shengjie Gao56, Levi Garraway82, Øystein Garred342, Erik Garrison49, Dale W. Garsed103, Nils Gehlenborg8,343, Josep L. l. Gelpi57,58, Joshy George110, Daniela S. Gerhard344, Clarissa Gerhauser345, Jeffrey E. Gershenwald346,347, Mark B. Gerstein5,18,19, Moritz Gerstung59,60, Gad Getz8,14,15,16, Mohammed Ghori49, Ronald Ghossein348, Nasra H. Giama349, Richard A. Gibbs12, Anthony J. Gill170,350, Pelvender Gill351, Dilip D. Giri348, Dominik Glodzik49, Vincent J. Gnanapragasam352,353, Maria Elisabeth Goebler354, Mary J. Goldman24, Carmen Gomez355, Santiago Gonzalez59,60, Abel Gonzalez-Perez298,299,356, Dmitry A. Gordenin357, James Gossage358, Kunihito Gotoh359, Ramaswamy Govindan3, Dorthe Grabau360, Janet S. Graham133,361, Robert C. Grant148,260, Anthony R. Green315, Eric Green27, Liliana Greger59, Nicola Grehan282, Sonia Grimaldi177, Sean M. Grimmond362, Robert L. Grossman363, Adam Grundhoff97,364, Gunes Gundem88, Qianyun Guo75, Manaswi Gupta8, Shailja Gupta365, Ivo G. Gut52,61, Marta Gut52,61, Jonathan Göke292,366, Gavin Ha8, Andrea Haake111, David Haan37, Siegfried Haas185, Kerstin Haase290, James E. Haber367, Nina Habermann60, Faraz Hach62,63, Syed Haider6, Natsuko Hama118, Freddie C. Hamdy351, Anne Hamilton267, Mark P. Hamilton368, Leng Han369, George B. Hanna370, Martin Hansmann371, Nicholas J. Haradhvala8,72, Olivier Harismendy102,372, Ivon Harliwong113, Arif O. Harmanci5,373, Eoghan Harrington374, Takanori Hasegawa375, David Haussler24,25, Steve Hawkins223, Shinya Hayami376, Shuto Hayashi375, D. Neil Hayes134,377,378, Stephen J. Hayes379,380, Nicholas K. Hayward211,311, Steven Hazell221, Yao He381, Allison P. Heath382, Simon C. Heath52,61, David Hedley300, Apurva M. Hegde38, David I. Heiman8, Michael C. Heinold47,48, Zachary Heins88, Lawrence E. Heisler152, Eva Hellstrom-Lindberg383, Mohamed Helmy384, Seong Gu Heo385, Austin J. Hepperla134, José María Heredia-Genestar386, Carl Herrmann47,48,387, Peter Hersey211, Julian M. Hess8,26, Holmfridur Hilmarsdottir320, Jonathan Hinton49, Satoshi Hirano388, Nobuyoshi Hiraoka389, Katherine A. Hoadley134,390, Asger Hobolth75,168, Ermin Hodzic78, Jessica I. Hoell182, Steve Hoffmann163,164,165,391, Oliver Hofmann392, Andrea Holbrook166, Aliaksei Z. Holik53, Michael A. Hollingsworth393, Oliver Holmes209,311, Robert A. Holt30, Chen Hong205,237, Eun Pyo Hong385, Jongwhi H. Hong394, Gerrit K. Hooijer395, Henrik Hornshøj73, Fumie Hosoda118, Yong Hou56,396, Volker Hovestadt397, William Howat352, Alan P. Hoyle134, Ralph H. Hruban149, Jianhong Hu12, Taobo Hu64, Xing Hua240, Kuan-lin Huang1,398, Mei Huang176, Mi Ni Huang179,180, Vincent Huang6, Yi Huang65,66, Wolfgang Huber60, Thomas J. Hudson272,399, Michael Hummel400, Jillian A. Hung246,247, David Huntsman401, Ted R. Hupp402, Jason Huse88, Matthew R. Huska403, Barbara Hutter43,67,68, Carolyn M. Hutter27, Daniel Hübschmann48,54,404,405,406, Christine A. Iacobuzio-Donahue348, Charles David Imbusch205, Marcin Imielinski407,408, Seiya Imoto375, William B. Isaacs409, Keren Isaev6,44, Shumpei Ishikawa410, Murat Iskar397, S. M. Ashiqul Islam244, Michael Ittmann411,412,413, Sinisa Ivkovic284, Jose M. G. Izarzugaza414, Jocelyne Jacquemier415, Valerie Jakrot211, Nigel B. Jamieson133,172,416, Gun Ho Jang148, Se Jin Jang417, Joy C. Jayaseelan12, Reyka Jayasinghe1 , Stuart R. Jefferys134, Karine Jegalian418, Jennifer L. Jennings419, Seung-Hyup Jeon250, Lara Jerman60,420, Yuan Ji421,422, Wei Jiao6, Peter A. Johansson311, Amber L. Johns170, Jeremy Johns272, Rory Johnson230,423, Todd A. Johnson183, Clemency Jolly290, Yann Joly424, Jon G. Jonasson320, Corbin D. Jones425, David R. Jones49, David T. W. Jones426,427, Nic Jones428, Steven J. M. Jones30, Jos Jonkers204, Young Seok Ju49,249, Hartmut Juhl429, Jongsun Jung69, Malene Juul73, Randi Istrup Juul73, Sissel Juul374, Natalie Jäger47, Rolf Kabbe47, Andre Kahles276,277,278,279,430, Abdullah Kahraman431,432,433, Vera B. Kaiser434, Hojabr Kakavand211, Sangeetha Kalimuthu148, Christof von Kalle405, Koo Jeong Kang91, Katalin Karaszi351, Beth Karlan435, Rosa Karlić436, Dennis Karsch437, Katayoon Kasaian29,30, Karin S. Kassahn113,438, Hitoshi Katai439, Mamoru Kato440, Hiroto Katoh410, Yoshiiku Kawakami93, Jonathan D. Kay117, Stephen H. Kazakoff209,311, Marat D. Kazanov441,442,443, Maria Keays59, Electron Kebebew444,445, Richard F. Kefford446, Manolis Kellis8,447, James G. Kench170,350,448, Catherine J. Kennedy246,247, Jules N. A. Kerssemakers47, David Khoo273, Vincent Khoo221, Narong Khuntikeo115,449, Ekta Khurana301,302,450,451, Helena Kilpinen117, Hark Kyun Kim452, Hyung-Lae Kim70, Hyung-Yong Kim415, Hyunghwan Kim250, Jaegil Kim8, Jihoon Kim453, Jong K. Kim454, Youngwook Kim455,456, Tari A. King457,458,459, Wolfram Klapper128, Kortine Kleinheinz47,48, Leszek J. Klimczak460, Stian Knappskog49,461, Michael Kneba437, Bartha M. Knoppers424, Youngil Koh462,463, Jan Komorowski305,464, Daisuke Komura410, Mitsuhiro Komura375, Gu Kong415, Marcel Kool426,465, Jan O. Korbel59,60, Viktoriya Korchina12, Andrey Korshunov465, Michael Koscher465, Roelof Koster466, Zsofia Kote-Jarai178, Antonios Koures244, Milena Kovacevic284, Barbara Kremeyer49, Helene Kretzmer164,165, Markus Kreuz467, Savitri Krishnamurthy99,468, Dieter Kube469, Kiran Kumar8, Pardeep Kumar221, Sushant Kumar5,19, Yogesh Kumar64, Ritika Kundra114,121, Kirsten Kübler8,14,72, Ralf Küppers470, Jesper Lagergren383,471, Phillip H. Lai166, Peter W. Laird472, Sunil R. Lakhani473, Christopher M. Lalansingh6, Emilie Lalonde6, Fabien C. Lamaze6, Adam Lambert351, Eric Lander8, Pablo Landgraf474,475, Luca Landoni115, Anita Langerød130, Andrés Lanzós230,231,423, Denis Larsimont476, Erik Larsson477, Mark Lathrop189, Loretta M. S. Lau478, Chris Lawerenz55, Rita T. Lawlor177, Michael S. Lawrence8,72,183, Alexander J. Lazar99,108, Xuan Le479, Darlene Lee30, Donghoon Lee5, Eunjung Alice Lee480, Hee Jin Lee417, Jake June-Koo Lee264,266, Jeong-Yeon Lee481, Juhee Lee482, Ming Ta Michael Lee340, Henry Lee-Six49, Kjong-Van Lehmann276,277,278,279,430, Hans Lehrach483, Dido Lenze400, Conrad R. Leonard209,311, Daniel A. Leongamornlert49,178, Ignaty Leshchiner8, Louis Letourneau484, Ivica Letunic71, Douglas A. Levine88,485, Lora Lewis12, Tim Ley486, Chang Li56,396, Constance H. Li6,44, Haiyan Irene Li30, Jun Li21, Lin Li56, Shantao Li5, Siliang Li56,396, Xiaobo Li56,396, Xiaotong Li5, Xinyue Li56, Yilong Li49, Han Liang21, Sheng-Ben Liang234, Peter Lichter68,397, Pei Lin8, Ziao Lin8,487, W. M. Linehan488, Ole Christian Lingjærde489, Dongbing Liu56,396, Eric Minwei Liu88,301,302, Fei-Fei Liu201,490, Fenglin Liu381,491, Jia Liu492, Xingmin Liu56,396, Julie Livingstone6, Dimitri Livitz8, Naomi Livni221, Lucas Lochovsky5,19,110, Markus Loeffler467, Georgina V. Long211, Armando Lopez-Guillermo493, Shaoke Lou5,19, David N. Louis72, Laurence B. Lovat117, Yiling Lu38, Yong-Jie Lu162,494, Youyong Lu495,496,497, Claudio Luchini167, Ilinca Lungu144,148, Xuemei Luo152, Hayley J. Luxton117, Andy G. Lynch223,315,498, Lisa Lype36, Cristina López111,112, Carlos López-Otín499, Eric Z. Ma64, Yussanne Ma30, Gaetan MacGrogan500, Shona MacRae501, Geoff Macintyre223, Tobias Madsen73, Kazuhiro Maejima184, Andrea Mafficini177, Dennis T. Maglinte166,502, Arindam Maitra174, Partha P. Majumder174, Luca Malcovati232, Salem Malikic62,78, Giuseppe Malleo115, Graham J. Mann211,246,503, Luisa Mantovani-Löffler504, Kathleen Marchal505,506, Giovanni Marchegiani115, Elaine R. Mardis1,193,507, Adam A. Margolin31, Maximillian G. Marin37, Florian Markowetz223,315, Julia Markowski403, Jeffrey Marks508, Tomas Marques-Bonet61,81,386,509, Marco A. Marra30, Luke Marsden351, John W. M. Martens332, Sancha Martin49,510, Jose I. Martin-Subero81,511, Iñigo Martincorena49, Alexander Martinez-Fundichely301,302,451 Yosef E. Maruvka8,26,72, R. Jay Mashl1,2, Charlie E. Massie223, Thomas J. Matthew37, Lucy Matthews178, Erik Mayer221,512, Simon Mayes513, Michael Mayo30, Faridah Mbabaali272, Karen McCune514, Ultan McDermott49, Patrick D. McGillivray19, Michael D. McLellan1,3,20, John D. McPherson148,272,515, John R. McPherson179,180, Treasa A. McPherson260, Samuel R. Meier8, Alice Meng516, Shaowu Meng134, Andrew Menzies49, Neil D. Merrett115,517, Sue Merson178, Matthew Meyerson8,14,82, William U. Meyerson4,5, Piotr A. Mieczkowski518, George L. Mihaiescu76, Sanja Mijalkovic284, Ana Mijalkovic Mijalkovic-Lazic284, Tom Mikkelsen519, Michele Milella253, Linda Mileshkin103, Christopher A. Miller1 , David K. Miller113,170, Jessica K. Miller272, Gordon B. Mills33,34, Ana Milovanovic57, Sarah Minner520, Marco Miotto115, Gisela Mir Arnau267, Lisa Mirabello240, Chris Mitchell103, Thomas J. Mitchell49,315,352, Satoru Miyano375, Naoki Miyoshi375, Shinichi Mizuno521, Fruzsina Molnár-Gábor522, Malcolm J. Moore300, Richard A. Moore30, Sandro Morganella49, Quaid D. Morris127,490, Carl Morrison523,524, Lisle E. Mose134, Catherine D. Moser349, Ferran Muiños298,299, Loris Mularoni298,299, Andrew J. Mungall30, Karen Mungall30, Elizabeth A. Musgrove133, Ville Mustonen525,526,527, David Mutch528, Francesc Muyas52,53,74, Donna M. Muzny12, Alfonso Muñoz59, Jerome Myers529, Ola Myklebost461, Peter Möller530, Genta Nagae89, Adnan M. Nagrial170, Hardeep K. Nahal-Bose76, Hitoshi Nakagama531, Hidewaki Nakagawa184, Hiromi Nakamura118, Toru Nakamura388, Kaoru Nakano184, Tannistha Nandi532, Jyoti Nangalia49, Mia Nastic284, Arcadi Navarro61,81,386, Fabio C. P. Navarro19, David E. Neal223,352, Gerd Nettekoven533, Felicity Newell209,311, Steven J. Newhouse59, Yulia Newton37, Alvin Wei Tian Ng534, Anthony Ng535, Jonathan Nicholson49, David Nicol221, Yongzhan Nie321,536, G. Petur Nielsen72, Morten Muhlig Nielsen73, Serena Nik-Zainal49,281,282,537, Michael S. Noble8, Katia Nones209,311, Paul A. Northcott538, Faiyaz Notta148,539, Brian D. O’Connor76,540, Peter O’Donnell541, Maria O’Donovan282, Sarah O’Meara49, Brian Patrick O’Neill542, J. Robert O’Neill543, David Ocana59, Angelica Ochoa88, Layla Oesper544, Christopher Ogden221, Hideki Ohdan93, Kazuhiro Ohi375, Lucila Ohno-Machado244, Karin A. Oien523,545, Akinyemi I. Ojesina546,547,548, Hidenori Ojima549, Takuji Okusaka550, Larsson Omberg551, Choon Kiat Ong552, Stephan Ossowski52,53,74, German Ott553, B. F. Francis Ouellette76,554, Christine P’ng6, Marta Paczkowska6, Salvatore Paiella115, Chawalit Pairojkul523, Marina Pajic170, Qiang Pan-Hammarström56,555, Elli Papaemmanuil49, Irene Papatheodorou59, Nagarajan Paramasivam43,47, Ji Wan Park385, Joong-Won Park556, Keunchil Park557,558, Kiejung Park559, Peter J. Park264,266, Joel S. Parker518, Simon L. Parsons124, Harvey Pass560, Danielle Pasternack272, Alessandro Pastore276, Ann-Marie Patch209,311, Iris Pauporté251, Antonio Pea115, John V. Pearson209,311, Chandra Sekhar Pedamallu8,14,82, Jakob Skou Pedersen73,75, Paolo Pederzoli115, Martin Peifer270, Nathan A. Pennell561, Charles M. Perou129,518, Marc D. Perry76,77, Gloria M. Petersen562, Myron Peto22, Nicholas Petrelli563, Robert Petryszak59, Stefan M. Pfister426,465,564, Mark Phillips424, Oriol Pich298,299, Hilda A. Pickett478, Todd D. Pihl565, Nischalan Pillay566, Sarah Pinder567, Mark Pinese170, Andreia V. Pinho568, Esa Pitkänen60, Xavier Pivot569, Elena Piñeiro-Yáñez95, Laura Planko533, Christoph Plass345, Paz Polak8,14,15, Tirso Pons570, Irinel Popescu571, Olga Potapova572, Aparna Prasad52, Shaun R. Preston573, Manuel Prinz47, Antonia L. Pritchard311, Stephenie D. Prokopec6, Elena Provenzano574, Xose S. Puente499, Sonia Puig176, Montserrat Puiggròs57, Sergio Pulido-Tamayo505,506, Gulietta M. Pupo246, Colin A. Purdie575, Michael C. Quinn209,311, Raquel Rabionet52,53,576, Janet S. Rader577, Bernhard Radlwimmer397, Petar Radovic284, Benjamin Raeder60, Keiran M. Raine49, Manasa Ramakrishna49, Kamna Ramakrishnan49, Suresh Ramalingam578, Benjamin J. Raphael579, W. Kimryn Rathmell580, Tobias Rausch60, Guido Reifenberger475, Jüri Reimand6,44, Jorge Reis-Filho348, Victor Reuter348, Iker Reyes-Salazar298, Matthew A. Reyna579, Sheila M. Reynolds36, Esther Rheinbay8,14,72, Yasser Riazalhosseini189, Andrea L. Richardson323, Julia Richter111,128, Matthew Ringel581, Markus Ringnér181, Yasushi Rino582, Karsten Rippe405, Jeffrey Roach583, Lewis R. Roberts349, Nicola D. Roberts49, Steven A. Roberts584, A. Gordon Robertson30, Alan J. Robertson113, Javier Bartolomé Rodriguez57, Bernardo Rodriguez-Martin104,105,106, F. Germán Rodríguez-González83,332, Michael H. A. Roehrl44,123,148,234,585,586, Marius Rohde587, Hirofumi Rokutan440, Gilles Romieu588, Ilse Rooman170, Tom Roques262, Daniel Rosebrock8, Mara Rosenberg8,72, Philip C. Rosenstiel589, Andreas Rosenwald590, Edward W. Rowe221,591, Romina Royo57, Steven G. Rozen179,180,592, Yulia Rubanova17,127, Mark A. Rubin423,593,594,595,596, Carlota Rubio-Perez298,299,597, Vasilisa A. Rudneva60, Borislav C. Rusev177, Andrea Ruzzenente598, Gunnar Rätsch276,277,278,279,280,430, Radhakrishnan Sabarinathan298,299,599, Veronica Y. Sabelnykova6, Sara Sadeghi30, S. Cenk Sahinalp62,78,79, Natalie Saini357, Mihoko Saito-Adachi440, Gordon Saksena8, Adriana Salcedo6, Roberto Salgado600, Leonidas Salichos5,19, Richard Sallari8, Charles Saller601, Roberto Salvia115, Michelle Sam272, Jaswinder S. Samra115,602, Francisco Sanchez-Vega114,121, Chris Sander276,603,604, Grant Sanders134, Rajiv Sarin605, Iman Sarrafi62,78, Aya Sasaki-Oku184, Torill Sauer489, Guido Sauter520, Robyn P. M. Saw211, Maria Scardoni167, Christopher J. Scarlett170,606, Aldo Scarpa177, Ghislaine Scelo194, Dirk Schadendorf68,607, Jacqueline E. Schein30, Markus B. Schilhabel589, Matthias Schlesner47,80, Thorsten Schlomm84,608, Heather K. Schmidt1 , Sarah-Jane Schramm246, Stefan Schreiber609, Nikolaus Schultz121, Steven E. Schumacher8,323, Roland F. Schwarz59,403,405,610, Richard A. Scolyer211,448,602, David Scott428, Ralph Scully611, Raja Seethala612, Ayellet V. Segre8,613, Iris Selander260, Colin A. Semple434, Yasin Senbabaoglu276, Subhajit Sengupta614, Elisabetta Sereni115, Stefano Serra585, Dennis C. Sgroi72, Mark Shackleton103, Nimish C. Shah352, Sagedeh Shahabi234, Catherine A. Shang329, Ping Shang211, Ofer Shapira8,323, Troy Shelton271, Ciyue Shen603,604, Hui Shen615, Rebecca Shepherd49, Ruian Shi490, Yan Shi134, Yu-Jia Shiah6, Tatsuhiro Shibata118,616, Juliann Shih8,82, Eigo Shimizu375, Kiyo Shimizu617, Seung Jun Shin618, Yuichi Shiraishi375, Tal Shmaya285, Ilya Shmulevich36, Solomon I. Shorser6, Charles Short59, Raunak Shrestha62, Suyash S. Shringarpure217, Craig Shriver619, Shimin Shuai6,126, Nikos Sidiropoulos83, Reiner Siebert112,620, Anieta M. Sieuwerts332, Lina Sieverling205,237, Sabina Signoretti202,621, Katarzyna O. Sikora177, Michele Simbolo138, Ronald Simon520, Janae V. Simons134, Jared T. Simpson6,17, Peter T. Simpson473, Samuel Singer115,458, Nasa Sinnott-Armstrong8,217, Payal Sipahimalani30, Tara J. Skelly390, Marcel Smid332, Jaclyn Smith622, Karen Smith-McCune514, Nicholas D. Socci276, Heidi J. Sofia27, Matthew G. Soloway134, Lei Song240, Anil K. Sood623,624,625, Sharmila Sothi626, Christos Sotiriou244, Cameron M. Soulette37, Paul N. Span627, Paul T. Spellman22, Nicola Sperandio177, Andrew J. Spillane211, Oliver Spiro8, Jonathan Spring628, Johan Staaf181, Peter F. Stadler163,164,165, Peter Staib629, Stefan G. Stark277,279,618,630, Lucy Stebbings49, Ólafur Andri Stefánsson631, Oliver Stegle59,60,632, Lincoln D. Stein6,126, Alasdair Stenhouse633, Chip Stewart8, Stephan Stilgenbauer634, Miranda D. Stobbe52,61, Michael R. Stratton49, Jonathan R. Stretch211, Adam J. Struck31, Joshua M. Stuart24,37, Henk G. Stunnenberg396,635, Hong Su56,396, Xiaoping Su99, Ren X. Sun6, Stephanie Sungalee60, Hana Susak52,53, Akihiro Suzuki89,636, Fred Sweep637, Monika Szczepanowski128, Holger Sültmann67,638, Takashi Yugawa617, Angela Tam30, David Tamborero298,299, Benita Kiat Tee Tan639, Donghui Tan518, Patrick Tan180,532,592,640, Hiroko Tanaka375, Hirokazu Taniguchi616, Tomas J. Tanskanen641, Maxime Tarabichi49,290, Roy Tarnuzzer220, Patrick Tarpey642, Morgan L. Taschuk152, Kenji Tatsuno89, Simon Tavaré223,643, Darrin F. Taylor113, Amaro Taylor-Weiner8, Jon W. Teague49, Bin Tean Teh180,592,640,644,645, Varsha Tembe246, Javier Temes104,105, Kevin Thai76, Sarah P. Thayer393, Nina Thiessen30, Gilles Thomas646, Sarah Thomas221, Alan Thompson221, Alastair M. Thompson633, John F. Thompson211, R. Houston Thompson647, Heather Thorne103, Leigh B. Thorne176, Adrian Thorogood424, Grace Tiao8, Nebojsa Tijanic284, Lee E. Timms272, Roberto Tirabosco648, Marta Tojo106, Stefania Tommasi649, Christopher W. Toon170, Umut H. Toprak48,650, David Torrents57,81, Giampaolo Tortora651,652, Jörg Tost653, Yasushi Totoki118, David Townend654, Nadia Traficante103, Isabelle Treilleux655,656, Jean-Rémi Trotta61, Lorenz H. P. Trümper469, Ming Tsao124,539, Tatsuhiko Tsunoda183,657,658,659, Jose M. C. Tubio104,105,106, Olga Tucker660, Richard Turkington661, Daniel J. Turner513, Andrew Tutt323, Masaki Ueno376, Naoto T. Ueno662, Christopher Umbricht151,213,663, Husen M. Umer305,664, Timothy J. Underwood665, Lara Urban59,60, Tomoko Urushidate616, Tetsuo Ushiku339, Liis Uusküla-Reimand666,667, Alfonso Valencia57,81, David J. Van Den Berg166, Steven Van Laere307, Peter Van Loo290,291, Erwin G. Van Meir668, Gert G. Van den Eynden307, Theodorus Van der Kwast123, Naveen Vasudev137, Miguel Vazquez57,669, Ravikiran Vedururu267, Umadevi Veluvolu518, Shankar Vembu490,670, Lieven P. C. Verbeke506,671, Peter Vermeulen307, Clare Verrill351,672, Alain Viari177, David Vicente57, Caterina Vicentini177, K. Vijay Raghavan365, Juris Viksna673, Ricardo E. Vilain674, Izar Villasante57, Anne Vincent-Salomon635, Tapio Visakorpi190, Douglas Voet8, Paresh Vyas311,351, Ignacio Vázquez-García49,86,675,676, Nick M. Waddell209, Nicola Waddell209,311, Claes Wadelius677, Lina Wadi6, Rabea Wagener111,112, Jeremiah A. Wala8,14,82, Jian Wang56, Jiayin Wang1,40,66, Linghua Wang12, Qi Wang465, Wenyi Wang21, Yumeng Wang21, Zhining Wang220, Paul M. Waring523, Hans-Jörg Warnatz483, Jonathan Warrell5,19, Anne Y. Warren352,678, Sebastian M. Waszak60, David C. Wedge49,294,679, Dieter Weichenhan345, Paul Weinberger680, John N. Weinstein38, Joachim Weischenfeldt60,83,84, Daniel J. Weisenberger166, Ian Welch681, Michael C. Wendl1,10,11, Johannes Werner47,85, Justin P. Whalley61,682, David A. Wheeler12,13, Hayley C. Whitaker117, Dennis Wigle683, Matthew D. Wilkerson518, Ashley Williams244, James S. Wilmott211, Gavin W. Wilson6,148, Julie M. Wilson148, Richard K. Wilson1,684, Boris Winterhoff685, Jeffrey A. Wintersinger17,127,384, Maciej Wiznerowicz686,687, Stephan Wolf688, Bernice H. Wong689, Tina Wong1,30, Winghing Wong690, Youngchoon Woo250, Scott Wood209,311, Bradly G. Wouters44, Adam J. Wright6, Derek W. Wright133,691, Mark H. Wright217, Chin-Lee Wu72, Dai-Ying Wu285, Guanming Wu692, Jianmin Wu170, Kui Wu56,396, Yang Wu179,180, Zhenggang Wu64, Liu Xi12, Tian Xia693, Qian Xiang76, Xiao Xiao66, Rui Xing497, Heng Xiong56,396, Qinying Xu209,311, Yanxun Xu694, Hong Xue64, Shinichi Yachida118,695, Sergei Yakneen60, Rui Yamaguchi375, Takafumi N. Yamaguchi6, Masakazu Yamamoto120, Shogo Yamamoto89, Hiroki Yamaue376, Fan Yang490, Huanming Yang56, Jean Y. Yang696, Liming Yang220, Lixing Yang697, Shanlin Yang306, Tsun-Po Yang270, Yang Yang369, Xiaotong Yao408,698, Marie-Laure Yaspo483, Lucy Yates49, Christina Yau156, Chen Ye56,396, Kai Ye40,41, Venkata D. Yellapantula20,86, Christopher J. Yoon249, Sung-Soo Yoon463, Fouad Yousif6, Jun Yu699, Kaixian Yu700, Willie Yu701, Yingyan Yu702, Ke Yuan223,510,703, Yuan Yuan21, Denis Yuen6, Takashi Yugawa617, Christina K. Yung76, Olga Zaikova704, Jorge Zamora49,104,105,106, Marc Zapatka397, Jean C. Zenklusen220, Thorsten Zenz67, Nikolajs Zeps705,706, Cheng-Zhong Zhang8,707, Fan Zhang381, Hailei Zhang8, Hongwei Zhang494, Hongxin Zhang121, Jiashan Zhang220, Jing Zhang5, Junjun Zhang76, Xiuqing Zhang56, Xuanping Zhang66,369, Yan Zhang5,708,709, Zemin Zhang381,710, Zhongming Zhao711, Liangtao Zheng381, Xiuqing Zheng381, Wanding Zhou615, Yong Zhou56, Bin Zhu240, Hongtu Zhu700,712, Jingchun Zhu24, Shida Zhu56,396, Lihua Zou713, Xueqing Zou49, Anna deFazio246,247,714, Nicholas van As221, Carolien H. M. van Deurzen715, Marc J. van de Vijver523, L. van’t Veer716 & Christian von Mering433,717, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.
- Published
- 2020
17. Genomic and Pathologic Profiling of Very Well-Differentiated Gastric Adenocarcinoma of Intestinal Type: A Study With Emphasis on Diffuse-Type Transformation.
- Author
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Rokutan H, Arai Y, Kunita A, Yamasaki S, Nakamura H, Hama N, Nakayama A, Hosoda F, Totoki Y, Fujishiro M, Seto Y, Shibata T, and Ushiku T
- Subjects
- Humans, Male, Female, Middle Aged, Aged, rhoA GTP-Binding Protein genetics, Cell Differentiation, Adult, Phenotype, Aged, 80 and over, Tumor Suppressor Protein p53 genetics, Genetic Predisposition to Disease, DNA Mutational Analysis, High-Throughput Nucleotide Sequencing, Stomach Neoplasms genetics, Stomach Neoplasms pathology, Adenocarcinoma genetics, Adenocarcinoma pathology, Adenocarcinoma chemistry, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic pathology, Mutation, Biomarkers, Tumor genetics, Biomarkers, Tumor analysis
- Abstract
Very well-differentiated adenocarcinoma of intestinal type is a distinct subtype of gastric cancer characterized by anastomosing glands with a hand-in-hand pattern and low-grade cytologic atypia resembling intestinal metaplasia. This is a slow-growing neoplasm with an indolent clinical course; however, a subset demonstrates transformation into adenocarcinoma with higher-grade histology, typically diffuse-type carcinoma, and behaves aggressively. This study aimed to better characterize the genomic and pathologic features, with a focus on factors associated with diffuse-type transformation. A total of 58 cases with (n=31) and without (n=27) diffuse-type transformation were analyzed for molecular and pathologic features. First, comprehensive deep DNA sequencing was conducted in 18 cases (discovery cohort), followed by a digital droplet polymerase chain reaction of hot spot RHOA mutations in 40 cases (validation cohort). In total, RHOA mutations were the most common alteration (34%), followed by loss of ARID1A (12%), p53 alterations (10%), and CLDN18 :: ARHGAP26/6 fusions (3.4%). FGFR2 amplification was identified in an advanced case with a p53 alteration. Altered p53 expression was recognized only in higher-grade components and was significantly associated with advanced disease ( P =0.0015) and diffuse-type transformation ( P =0.026). A mixed mucin phenotype was also strongly correlated with advanced disease ( P <0.001) and diffuse-type transformation ( P <0.001). Decreased E-cadherin expression was frequently observed (74%) in poorly cohesive components. This study demonstrated that a subset of RHOA -mutant diffuse-type gastric cancers develops through the transformation of very well-differentiated adenocarcinoma of intestinal type. Our observations suggest a mixed mucin phenotype as a risk factor and alterations in p53 and E-cadherin as drivers of diffuse-type transformation., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2024
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18. Oncogenic structural aberration landscape in gastric cancer genomes.
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Saito-Adachi M, Hama N, Totoki Y, Nakamura H, Arai Y, Hosoda F, Rokutan H, Yachida S, Kato M, Fukagawa A, and Shibata T
- Subjects
- Humans, BRCA1 Protein, BRCA2 Protein, Stomach Neoplasms genetics
- Abstract
Structural variants (SVs) are responsible for driver events in gastric cancer (GC); however, their patterns and processes remain poorly understood. Here, we examine 170 GC whole genomes to unravel the oncogenic structural aberration landscape in GC genomes and identify six rearrangement signatures (RSs). Non-random combinations of RSs elucidate distinctive GC subtypes comprising one or a few dominant RS that are associated with specific driver events (BRCA1/2 defects, mismatch repair deficiency, and TP53 mutation) and epidemiological backgrounds. Twenty-seven SV hotspots are identified as GC driver candidates. SV hotspots frequently constitute complexly clustered SVs involved in driver gene amplification, such as ERBB2, CCNE1, and FGFR2. Further deconstruction of the locally clustered SVs uncovers amplicon-generating profiles characterized by super-large SVs and intensive segmental amplifications, contributing to the extensive amplification of GC oncogenes. Comprehensive analyses using adjusted SV allele frequencies indicate the significant involvement of extra-chromosomal DNA in processes linked to specific RSs., (© 2023. The Author(s).)
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- 2023
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19. Multiancestry genomic and transcriptomic analysis of gastric cancer.
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Totoki Y, Saito-Adachi M, Shiraishi Y, Komura D, Nakamura H, Suzuki A, Tatsuno K, Rokutan H, Hama N, Yamamoto S, Ono H, Arai Y, Hosoda F, Katoh H, Chiba K, Iida N, Nagae G, Ueda H, Shihang C, Sekine S, Abe H, Nomura S, Matsuura T, Sakai E, Ohshima T, Rino Y, Yeoh KG, So J, Sanghvi K, Soong R, Fukagawa A, Yachida S, Kato M, Seto Y, Ushiku T, Nakajima A, Katai H, Tan P, Ishikawa S, Aburatani H, and Shibata T
- Subjects
- Humans, Transcriptome, Herpesvirus 4, Human genetics, Genomics, Stomach Neoplasms pathology, Epstein-Barr Virus Infections complications, Epstein-Barr Virus Infections genetics
- Abstract
Gastric cancer is among the most common malignancies worldwide, characterized by geographical, epidemiological and histological heterogeneity. Here, we report an extensive, multiancestral landscape of driver events in gastric cancer, involving 1,335 cases. Seventy-seven significantly mutated genes (SMGs) were identified, including ARHGAP5 and TRIM49C. We also identified subtype-specific drivers, including PIGR and SOX9, which were enriched in the diffuse subtype of the disease. SMGs also varied according to Epstein-Barr virus infection status and ancestry. Non-protein-truncating CDH1 mutations, which are characterized by in-frame splicing alterations, targeted localized extracellular domains and uniquely occurred in sporadic diffuse-type cases. In patients with gastric cancer with East Asian ancestry, our data suggested a link between alcohol consumption or metabolism and the development of RHOA mutations. Moreover, mutations with potential roles in immune evasion were identified. Overall, these data provide comprehensive insights into the molecular landscape of gastric cancer across various subtypes and ancestries., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
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- 2023
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20. Comprehensive biomarker analysis from phase II study of nivolumab in patients with thymic carcinoma.
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Katsuya Y, Kitano S, Yamashita M, Ouchi M, Yagishita S, Hamada A, Nakamura H, Hosoda F, Shibata T, Motoi N, Nakayama T, Seto T, Umemura S, Hosomi Y, Satouchi M, Nishio M, Kozuki T, Hida T, Ohe Y, and Horinouchi H
- Abstract
In a phase II trial of nivolumab in advanced thymic carcinoma (UMIN000022007), long SD (SD for more than 24 weeks) was seen in three patients and irAE (Gr2 or higher) was seen in four patients among 15 patients. Here, we report preplanned comprehensive biomarker analyses. We obtained tumor samples for immunohistochemistry, peripheral blood mononuclear cells (PBMCs), plasma and serum for pharmacokinetic analysis of nivolumab and cytokine evaluations, and whole blood for immuno pharmacogenomic (PGx) analysis. PD-L1 expression on tumor cells were not associated with therapeutic efficacy, but FOXP3 expression in tumor area and stroma, CD204 expression in stroma, and MHC class I in tumor area were all low among long SD patients. PBMC of long SD patients presented with larger number of naïve/memory cells prior to treatment, suggesting priming after nivolumab administration. Immuno-PGx analysis showed non-synonymous SNVs in ITGAX and PDCD1 had some correlation with PFS. Concentration of nivolumab in blood during the treatment was not related to PFS, with their overall trend towards decreased nivolumab concentration in patients with irAEs. Low immunogenicity of thymic carcinoma demonstrated in our study may require the activation of immune systems via a combination of immune checkpoint blockades., Competing Interests: SK reports grants and personal fees from Astra Zeneca, grants and personal fees from Pfizer, grants and personal fees from Boehringer Ingelheim, personal fees from Taiho, personal fees from Novartis, grants and personal fees from MSD, personal fees from Sumitomo Dainippon Pharma, grants and personal fees from Eisai, grants from Astellas, grants from Gilead Sciences, grants and personal fees from Ono Pharmaceutical Co., Ltd., personal fees from Bristol-Myers Squibb, grants and personal fees from REGENERON, personal fees from Rakuten Medical, grants from PACT Pharma, grants from Takara Bio Inc., personal fees from GSK, grants and personal fees from Daiichi-Sankyo, grants and personal fees from Chugai, personal fees from ImmuniT Research Inc., grants from AMED(Japan Agency for Medical Research and Development), grants from JSPS(Japan Society for the Promotion of Science), personal fees from PMDA(Pharmaceuticals and Medical Devices Agency), outside the submitted work. SY reports grants from Nippon Boheringer Ingelheim, outside the submitted work. AH reports Grants or contracts from Eisai, Healios, Eli Lilly, Daiichi Sankyo, Chordia Therapeutics, Konica Minolta, outside the submitted work. TSe reports Grants or contracts from Abbvie, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, MSD, Novartis Pharma. Pfizer Japan, Takeda Pharmaceutical, and Payment of honoraria from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Covidien Japan, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical, Towa Pharmaceutical, and other interests from Precision Medicine Asia, outside the submitted work. SU reports Payment of honoraria from Chugai Pharmaceutical, outside the submitted work. YH reports Payment of honoraria from AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Eisai, outside the submitted work. MS reports Grants or contracts from Ono, Bristol Myers Squibb, Chugai, MSD, IQVIA, EPS, Janssen, Amgen, Taiho, Pfizer, Abbvie, Daiichi-Sankyo, Takeda, Eisai, and Payment of honoraria from Ono, Bristol Myers Squibb, Chugai, MSD, AstraZeneca, Eli Lilly, Taiho, Pfizer, Novartis, Takeda, Merck, outside the submitted work. MN reports grants and personal fees from Ono Pharmaceutical, grants and personal fees from Bristol Myers Squibb, grants and personal fees from Pfizer, grants and personal fees from Chugai Pharmaceutical, grants and personal fees from Eli Lilly, grants and personal fees from Taiho Pharmaceutical, grants and personal fees from AstraZeneca, personal fees from Boehringer-Ingelheim, grants and personal fees from MSD, grants and personal fees from Novartis, personal fees from Merck Biopharma, grants and personal fees from Daiichi Sankyo, grants and personal fees from Takeda Pharmaceutical Company Limited, personal fees from Teijin Pharma Limited., personal fees from AbbVie, outside the submitted work. TK reports Consulting fees from Chugai Pharmaceutical Co., AstraZeneca, Ono Pharmaceutical Co., Pfizer Japan, Daiichi-Sankyo, Bayer, Abbvie, and Payment of honoraria from Chugai Pharmaceutical Co., AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical Co., Bristol-Myers Squibb, Ono Pharmaceutical Co., MSD, Pfizer Japan, Kyowa Hakko Kirin, Nippon Beohringer Ingelheim, Merck Biophama, Nippon Kayaku, Novartis, Daiichi-Sankyo, Takeda Pharmaceutical Co., Bayer, Sawai, outside the submitted work. TH reports Payment or honoraria from ONO Pharmaceutical, Bristol-Meyers Squibb, MSD, outside the submitted work. YO is an editorial board member, and reports Grants or contracts from AstraZeneca, Chugai, Lilly, ONO, BMS, Kyorin, Dainippon- Sumitomo, Pfizer, Taiho, Novartis, Takeda, Kissei, Daiichi-Sankyo, Janssen, LOXO, and Payment or honoraria from AstraZeneca, Chugai, Eli Lilly, ONO, BMS,Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Hakko Kirin, and Payment for expert testimony from AstraZeneca, Chugai, ONO, BMS, Kyorin, Celltrion, Amgen, Nippon Kayaku, Boehringer Ingelheim, AnHeart Therapeutics Inc., and Leadership or fiduciary role in JSMO, JLCS, JCOG, outside the submitted work. HH reports Grants or contracts from MSD, Abbvie, AstraZeneca, BMS, Ono, Merck Biophama, Daiichi-Sankyo, Janssen, Genomic Helath, Chugai, Roche, and Novartis, and Payments or honoraria from AstraZeneca, MSD, Eli Lilly, Ono, BMS, Chugai, Roche, Kyowa-Kirin, and Novartis, and Participation on an Advisory board for AstraZeneca, Eli Lilly, Chugai, Roche, ONO, BMS, and MSD, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Katsuya, Kitano, Yamashita, Ouchi, Yagishita, Hamada, Nakamura, Hosoda, Shibata, Motoi, Nakayama, Seto, Umemura, Hosomi, Satouchi, Nishio, Kozuki, Hida, Ohe and Horinouchi.)
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- 2023
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21. Pharmacokinetic and pharmacogenomic analysis of low-dose afatinib treatment in elderly patients with EGFR mutation-positive non-small cell lung cancer.
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Mizugaki H, Oizumi S, Fujita Y, Harada T, Nakahara Y, Takashina T, Ko R, Watanabe K, Hotta T, Minemura H, Saeki S, Asahina H, Nakamura K, Nakamura H, Hosoda F, Yagishita S, and Hamada A
- Subjects
- Afatinib therapeutic use, Aged, Carcinoma, Non-Small-Cell Lung mortality, Female, Humans, Lung Neoplasms mortality, Male, Progression-Free Survival, Protein Kinase Inhibitors therapeutic use, Afatinib pharmacokinetics, Afatinib pharmacology, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Protein Kinase Inhibitors pharmacokinetics, Protein Kinase Inhibitors pharmacology
- Abstract
Purpose: An increasing number of advanced non-small cell lung cancer (NSCLC) cases are being reported in the ageing population. However, studies on the use of afatinib in elderly patients are scarce. We conducted a prospective multicentre, single-arm, and open-label phase II trial for low-dose afatinib (30 mg/day) use in elderly patients with NSCLC with EGFR mutation to assess quality-of-life (QOL) and pharmacokinetic (PK)/pharmacogenomic (PGx) parameters., Patients and Methods: The primary end-point was the objective response rate (ORR), and the planned number of registered cases was 35, with a threshold ORR of 50%, an expected ORR of 75%, α of 0.05, and β of 0.1. Secondary end-points were progression-free survival (PFS), overall survival (OS), the incidence rate of adverse events (AEs), QOL survey (FACT-L), and trough plasma concentration of afatinib at steady state (Css) and at the occurrence of clinically significant AEs., Results: The median age of the patients was 79 years. The ORR was 80.0% and the disease control rate was 91.4%. The median PFS and OS were 15.6 and 29.5 months, respectively. Four patients discontinued because of AEs. Treatment-related death was not observed. No significant change in QOL was observed at baseline and after 4, 8, and 12 weeks. Css was comparable with those in previous reports and was significantly higher in patients with grade 3 AEs. Direct correlations between afatinib treatment and PGx profiles were not observed., Conclusions: An afatinib starting dose of 30 mg/day could be an effective and safe treatment option for elderly patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
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- 2022
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22. DNA Adductome Analysis Identifies N -Nitrosopiperidine Involved in the Etiology of Esophageal Cancer in Cixian, China.
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Totsuka Y, Lin Y, He Y, Ishino K, Sato H, Kato M, Nagai M, Elzawahry A, Totoki Y, Nakamura H, Hosoda F, Shibata T, Matsuda T, Matsushima Y, Song G, Meng F, Li D, Liu J, Qiao Y, Wei W, Inoue M, Kikuchi S, Nakagama H, and Shan B
- Subjects
- Administration, Oral, Adult, Aged, Animals, China, Chromatography, Liquid, DNA chemistry, DNA isolation & purification, Esophageal Neoplasms chemically induced, Esophageal Neoplasms etiology, Female, Humans, Male, Mass Spectrometry, Middle Aged, Nitrosamines administration & dosage, Rats, Rats, Inbred F344, DNA Adducts analysis, Esophageal Neoplasms diagnosis, Nitrosamines analysis
- Abstract
Esophageal cancer is prevalent in Cixian, China, but the etiology of this disease remains largely unknown. Therefore, we explored this by conducting a DNA adductome analysis. Both tumorous and nontumorous tissues were collected from patients who underwent surgical procedures at Cixian Cancer Hospital and the Fourth Hospital of Hebei Medical University, which is in a low-incidence area. N
2 -(3,4,5,6-Tetrahydro-2 H -pyran-2-yl)deoxyguanosine (THP-dG) was the major adduct detected in samples from esophageal cancer patients in Cixian. The precursor of THP-dG, N -nitrosopiperidine (NPIP), exhibited a strong mutagenic activity under metabolic activation in the Ames test and a significant dose-dependent increase in mutation frequency during an in vivo mutagenicity test with guanine phosphoribosyltransferase ( gpt ) delta rats. The NPIP-induced mutation was dominated by A:T to C:G transversions, followed by G:C to A:T and A:T to G:C transitions, in the liver and esophagus of animal samples. A similar mutational pattern was observed in the mutational signature of esophageal cancer patients that demonstrated weak correlation with THP-dG levels. These findings suggested that NPIP exposure is partly involved in the development of esophageal cancer in Cixian residents.- Published
- 2019
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23. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer.
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Yachida S, Mizutani S, Shiroma H, Shiba S, Nakajima T, Sakamoto T, Watanabe H, Masuda K, Nishimoto Y, Kubo M, Hosoda F, Rokutan H, Matsumoto M, Takamaru H, Yamada M, Matsuda T, Iwasaki M, Yamaji T, Yachida T, Soga T, Kurokawa K, Toyoda A, Ogura Y, Hayashi T, Hatakeyama M, Nakagama H, Saito Y, Fukuda S, Shibata T, and Yamada T
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- Adult, Aged, Case-Control Studies, Colorectal Neoplasms genetics, Disease Progression, Female, Humans, Male, Metabolomics, Metagenomics, Middle Aged, Neoplasm Staging, Young Adult, Colorectal Neoplasms metabolism, Colorectal Neoplasms microbiology, Gastrointestinal Microbiome genetics
- Abstract
In most cases of sporadic colorectal cancers, tumorigenesis is a multistep process, involving genomic alterations in parallel with morphologic changes. In addition, accumulating evidence suggests that the human gut microbiome is linked to the development of colorectal cancer. Here we performed fecal metagenomic and metabolomic studies on samples from a large cohort of 616 participants who underwent colonoscopy to assess taxonomic and functional characteristics of gut microbiota and metabolites. Microbiome and metabolome shifts were apparent in cases of multiple polypoid adenomas and intramucosal carcinomas, in addition to more advanced lesions. We found two distinct patterns of microbiome elevations. First, the relative abundance of Fusobacterium nucleatum spp. was significantly (P < 0.005) elevated continuously from intramucosal carcinoma to more advanced stages. Second, Atopobium parvulum and Actinomyces odontolyticus, which co-occurred in intramucosal carcinomas, were significantly (P < 0.005) increased only in multiple polypoid adenomas and/or intramucosal carcinomas. Metabolome analyses showed that branched-chain amino acids and phenylalanine were significantly (P < 0.005) increased in intramucosal carcinomas and bile acids, including deoxycholate, were significantly (P < 0.005) elevated in multiple polypoid adenomas and/or intramucosal carcinomas. We identified metagenomic and metabolomic markers to discriminate cases of intramucosal carcinoma from the healthy controls. Our large-cohort multi-omics data indicate that shifts in the microbiome and metabolome occur from the very early stages of the development of colorectal cancer, which is of possible etiological and diagnostic importance.
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- 2019
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24. Initial and crucial genetic events in intestinal-type gastric intramucosal neoplasia.
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Rokutan H, Abe H, Nakamura H, Ushiku T, Arakawa E, Hosoda F, Yachida S, Tsuji Y, Fujishiro M, Koike K, Totoki Y, Fukayama M, and Shibata T
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- Aged, Aged, 80 and over, Carcinogenesis genetics, Cell Transformation, Neoplastic genetics, Female, Gastric Mucosa pathology, High-Throughput Nucleotide Sequencing methods, Humans, Loss of Heterozygosity genetics, Male, Middle Aged, Precancerous Conditions genetics, Precancerous Conditions pathology, Stomach Neoplasms pathology, Genes, APC physiology, Mutation genetics, Stomach Neoplasms genetics, Tumor Suppressor Protein p53 genetics
- Abstract
Gastric cancer (GC) is one of the most common and life-threatening malignancies. The course of disease and tumor aggressiveness vary among GCs, although how early fate is determined and by what factors remains elusive. To solve this question, we collected 43 gastric intramucosal neoplasias (GINs), comprising dysplasia/intraepithelial neoplasia (D/IEN; a premalignant lesion) and minute GC (miGC; ≤10 mm) of intestinal histotype and performed targeted deep DNA sequencing of 67 GC-related genes derived from large-scale data. Gastric D/IEN was classified into low or high grade (LG-D/IEN or HG-D/IEN). The most frequent mutations in D/IENs included APC (19/25; 76%), ARID2 (6/25; 24%) and MUC6 (5/25; 20%). All LG-D/IENs had APC mutation (12/12) and APC hotspot mutations affecting R1450 and E1554 were noted in both LG-D/IEN and HG-D/IEN. ARID2 mutation always co-occurred with APC mutation, whose tumor variant allele frequency (TVAF) was higher than that of ARID2 in D/IEN. APC and TP53 mutations were mutually exclusive in D/IEN (p = 0.031 [main cohort], p = 0.025 [expanding cohort]) and TP53-mutated D/IEN was exclusively HG-D/IEN (4/4). TP53 mutations were highly recurrent (11/14; 79%) in MLH1-positive miGCs and were detected even in two microscopic lesions measuring 1 and 3 mm, respectively. Furthermore, TVAF analyses suggested that TP53 mutation is the initial event in the TP53-mutated miGCs. In contrast, TP53 mutation was absent (0/4) in MLH1-negative small intramucosal carcinoma (8-24 mm). Advanced GC data suggested that early mutations (APC and TP53) may affect the potential of cancerous progression from D/IEN. This study revealed somatic mutational landscape and initial mutations of GINs, and we report for the first time that TP53 mutations precede other mutations in intestinal-type GC. Our results also indicate that molecular subtyping based on APC/TP53 mutations would be a high-priority approach for determining and predicting the malignant potential of GIN, including D/IEN. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
- Published
- 2019
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25. Exploration of germline variants responsible for adverse events of crizotinib in anaplastic lymphoma kinase-positive non-small cell lung cancer by target-gene panel sequencing.
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Mizugaki H, Hamada A, Shibata T, Hosoda F, Nakamura H, Okuma Y, Shukuya T, Umemura S, Horiike A, Fukui T, Kogure Y, Daga H, Urata Y, Yamada K, Saeki S, Fujisaka Y, Nakamura Y, Sato M, Yoshida T, Hotta T, Oizumi S, Fujiwara Y, Ohe Y, and Fujiwara Y
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- Adult, Aged, Aged, 80 and over, Amino Acid Substitution, Carcinoma, Non-Small-Cell Lung complications, Carcinoma, Non-Small-Cell Lung drug therapy, Crizotinib therapeutic use, Drug-Related Side Effects and Adverse Reactions diagnosis, Female, Germ-Line Mutation, High-Throughput Nucleotide Sequencing, Humans, Lung Neoplasms complications, Lung Neoplasms drug therapy, Male, Middle Aged, Neoplasm Staging, Polymorphism, Single Nucleotide, Protein Kinase Inhibitors therapeutic use, Anaplastic Lymphoma Kinase genetics, Carcinoma, Non-Small-Cell Lung genetics, Crizotinib adverse effects, Drug-Related Side Effects and Adverse Reactions genetics, Lung Neoplasms genetics, Pharmacogenomic Variants genetics, Protein Kinase Inhibitors adverse effects
- Abstract
Objectives: Crizotinib is a standard treatment for advanced anaplastic lymphoma kinase (ALK)- or ROS1-fusion-gene-positive non-small cell lung cancer; however, serious adverse events (AEs), including elevated alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and interstitial lung disease (ILD), develop occasionally. Here, we evaluated relationships between clinically significant crizotinib-associated AEs and germline variations., Materials and Methods: DNA obtained from 75 patients allowed selection of 147 genes according to function, exon identification and sequencing, and determination of germline single nucleotide variants (SNVs). Correlations between clinically significant AEs and presence of germline variants were estimated by Fisher's exact test., Results: We defined clinically significant AEs as grade 4 hematological toxicity, grade ≥3 non-hematological toxicity, and any grade of ILD. These AEs were observed in 26 patients (35%), with elevated AST/ALT (15%) the most common, followed by neutropenia (5%), ILD (4%), and thromboembolic events (4%). Nonsynonymous SNVs in epoxide hydrolase 1 (EPHX1) [odds ratio (OR): 3.86; p = 0.0009) and transcription factor 7-like 2 (TCF7L2) (OR: 2.51; p = 0.025) were associated with the presence of clinically significant AEs., Conclusion: Nonsynonymous EPHX1 and TCF7L2 SNVs might be associated with clinically significant crizotinib-associated AEs. These data indicated that target-gene sequencing could be feasible for predicting anticancer-agent toxicity, and that germline multi-gene information might be useful for predicting patient-specific AEs to promote precision medicine., (Copyright © 2018 Elsevier B.V. All rights reserved.)
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- 2019
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26. Integrated genetic and epigenetic analysis of myxofibrosarcoma.
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Ogura K, Hosoda F, Arai Y, Nakamura H, Hama N, Totoki Y, Yoshida A, Nagai M, Kato M, Arakawa E, Mukai W, Rokutan H, Kawai A, Tanaka S, and Shibata T
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- Animals, Cohort Studies, Fibroma metabolism, Fibroma mortality, Fibroma pathology, Fibrosarcoma metabolism, Fibrosarcoma mortality, Fibrosarcoma pathology, Heterografts, Humans, Janus Kinase 1 genetics, Janus Kinase 1 metabolism, Mice, Mice, Nude, Monosaccharide Transport Proteins genetics, Monosaccharide Transport Proteins metabolism, Mutation, Neurofibromin 1 genetics, Neurofibromin 1 metabolism, Oncogene Proteins, Fusion metabolism, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins B-raf metabolism, Receptor, trkA genetics, Receptor, trkA metabolism, Survival Analysis, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Exome Sequencing, X-linked Nuclear Protein genetics, X-linked Nuclear Protein metabolism, Epigenesis, Genetic, Fibroma genetics, Fibrosarcoma genetics, Gene Expression Regulation, Neoplastic, Genes, cdc, Oncogene Proteins, Fusion genetics
- Abstract
Myxofibrosarcoma (MFS) is a common adult soft tissue sarcoma characterized by an infiltrative growth pattern and a high local recurrence rate. Here we report the genetic and epigenetic landscape of MFS based on the results of whole-exome sequencing (N = 41), RNA sequencing (N = 29), and methylation analysis (N = 41), using 41 MFSs as a discovery set, and subsequent targeted sequencing of 140 genes in the entire cohort of 99 MFSs and 17 MFSs' data from TCGA. Fourteen driver genes are identified, including potentially actionable therapeutic targets seen in 37% of cases. There are frequent alterations in p53 signaling (51%) and cell cycle checkpoint genes (43%). Other conceivably actionable driver genes including ATRX, JAK1, NF1, NTRK1, and novel oncogenic BRAF fusion gene are identified. Methylation patterns cluster into three subtypes associated with unique combinations of driver mutations, clinical outcomes, and immune cell compositions. Our results provide a valuable genomic resource to enable the design of precision medicine for MFS.
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- 2018
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27. Epigenetic landscape influences the liver cancer genome architecture.
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Hama N, Totoki Y, Miura F, Tatsuno K, Saito-Adachi M, Nakamura H, Arai Y, Hosoda F, Urushidate T, Ohashi S, Mukai W, Hiraoka N, Aburatani H, Ito T, and Shibata T
- Subjects
- Adult, Aged, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular virology, Chromatin genetics, Chromatin metabolism, DNA Methylation, Epigenomics, Female, Genome, Viral, Hepatitis B virus genetics, Hepatitis B virus physiology, Humans, Liver Neoplasms virology, Male, Middle Aged, Mutation, Virus Integration, Genome, Human, Liver Neoplasms genetics
- Abstract
The accumulations of different types of genetic alterations such as nucleotide substitutions, structural rearrangements and viral genome integrations and epigenetic alterations contribute to carcinogenesis. Here, we report correlation between the occurrence of epigenetic features and genetic aberrations by whole-genome bisulfite, whole-genome shotgun, long-read, and virus capture sequencing of 373 liver cancers. Somatic substitutions and rearrangement breakpoints are enriched in tumor-specific hypo-methylated regions with inactive chromatin marks and actively transcribed highly methylated regions in the cancer genome. Individual mutation signatures depend on chromatin status, especially, signatures with a higher transcriptional strand bias occur within active chromatic areas. Hepatitis B virus (HBV) integration sites are frequently detected within inactive chromatin regions in cancer cells, as a consequence of negative selection for integrations in active chromatin regions. Ultra-high structural instability and preserved unmethylation of integrated HBV genomes are observed. We conclude that both precancerous and somatic epigenetic features contribute to the cancer genome architecture.
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- 2018
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28. Highly recurrent H3F3A mutations with additional epigenetic regulator alterations in giant cell tumor of bone.
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Ogura K, Hosoda F, Nakamura H, Hama N, Totoki Y, Yoshida A, Ohashi S, Rokutan H, Takai E, Yachida S, Kawai A, Tanaka S, and Shibata T
- Subjects
- Adult, Bone Neoplasms pathology, Case-Control Studies, Female, Giant Cell Tumor of Bone pathology, Humans, Male, Bone Neoplasms genetics, Epigenesis, Genetic, Giant Cell Tumor of Bone genetics, Histones genetics, Mutation, Missense
- Abstract
Recurrent H3F3A and IDH2 mutations have been reported in giant cell tumor of bone (GCTB). However, the reported incidences have varied, and other molecular genetic alterations have not been identified due to the small number of cases analyzed with comprehensive methods. Moreover, the relative sensitivities of Sanger sequencing and next-generation sequencing (NGS) for the detection of H3F3A mutations in DNA extracted from archival formalin-fixed paraffin-embedded (FFPE) samples for clinical diagnosis have not been assessed. To address these issues, we conducted whole-exome sequencing of 7 GCTBs and integrated the previously published genomic sequencing data of 6 GCTBs. We subsequently performed targeted sequencing of an additional 39 GCTBs, including 2 atypical cases and an extremely rare case of primary malignant transformation of GCTB. We also evaluated the sensitivity of Sanger sequencing for detecting H3F3A mutations in FFPE samples that are usually used for clinical diagnosis. H3F3A glycine hotspot mutations were the most frequently detected mutations (96%) in the 52 GCTBs by NGS. Of the 50 hotspot mutations, p.G34W was observed in 48 cases and p.G34L/G34R was detected in one. One of two atypical GCTB cases with wild-type H3F3A had a H3F3B mutation (p.G34V). Other mutated genes were not recurrent. Sanger sequencing did not detect H3F3A mutations in 10 of 15 H3F3A NGS mutation-positive FFPE samples. In conclusion, we confirmed that H3F3A is the most frequently mutated GCTB driver gene, and that H3F3A mutations are not present in atypical GCTBs. Sanger sequencing was much less sensitive than targeted NGS for detecting H3F3A mutations in FFPE samples., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2017
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29. Comprehensive mutation profiling of mucinous gastric carcinoma.
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Rokutan H, Hosoda F, Hama N, Nakamura H, Totoki Y, Furukawa E, Arakawa E, Ohashi S, Urushidate T, Satoh H, Shimizu H, Igarashi K, Yachida S, Katai H, Taniguchi H, Fukayama M, and Shibata T
- Subjects
- Adenocarcinoma, Mucinous pathology, Aged, Aged, 80 and over, DNA Mutational Analysis, Female, Humans, Male, Middle Aged, Stomach Neoplasms pathology, Adenocarcinoma, Mucinous genetics, Mutation, Stomach Neoplasms genetics
- Abstract
Mucinous gastric carcinoma (MGC) is a unique subtype of gastric cancer with a poor survival outcome. Comprehensive molecular profiles and putative therapeutic targets of MGC remain undetermined. We subjected 16 tumour-normal tissue pairs to whole-exome sequencing (WES) and an expanded set of 52 tumour-normal tissue pairs to subsequent targeted sequencing. The latter focused on 114 genes identified by WES. Twenty-two histologically differentiated MGCs (D-MGCs) and 46 undifferentiated MGCs (U-MGCs) were analysed. Chromatin modifier genes, including ARID1A (21%), MLL2 (19%), MLL3 (15%), and KDM6A (7%), were frequently mutated (47%) in MGC. We also identified mutations in potential therapeutic target genes, including MTOR (9%), BRCA2 (9%), BRCA1 (7%), and ERBB3 (6%). RHOA mutation was detected only in 4% of U-MGCs and in no D-MGCs. MYH9 was recurrently (13%) mutated in MGC, with all these being of the U-MGC subtype (p = 0.023). Three U-MGCs harboured MYH9 nonsense mutations. MYH9 knockdown enhanced cell migration and induced intracytoplasmic mucin and cellular elongation. BCOR mutation was associated with improved survival. In U-MGCs, the MLH1 expression status and combined mutation status (TP53/BCL11B or TP53/MLL2) were prognostic factors. A comparative analysis of driver genes revealed that the mutation profile of D-MGC was similar to that of intestinal-type gastric cancer, whereas U-MGC was a distinct entity, harbouring a different mutational profile to intestinal- and diffuse-type gastric cancers. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
- Published
- 2016
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30. High stability of faecal microbiome composition in guanidine thiocyanate solution at room temperature and robustness during colonoscopy.
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Nishimoto Y, Mizutani S, Nakajima T, Hosoda F, Watanabe H, Saito Y, Shibata T, Yachida S, and Yamada T
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- Colonoscopy, Feces, Guanidines, Thiocyanates, Microbiota, Temperature
- Published
- 2016
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31. Recurrent neomorphic mutations of MTOR in central nervous system and testicular germ cell tumors may be targeted for therapy.
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Ichimura K, Fukushima S, Totoki Y, Matsushita Y, Otsuka A, Tomiyama A, Niwa T, Takami H, Nakamura T, Suzuki T, Fukuoka K, Yanagisawa T, Mishima K, Nakazato Y, Hosoda F, Narita Y, Shibui S, Yoshida A, Mukasa A, Saito N, Kumabe T, Kanamori M, Tominaga T, Kobayashi K, Shimizu S, Nagane M, Iuchi T, Mizoguchi M, Yoshimoto K, Tamura K, Maehara T, Sugiyama K, Nakada M, Sakai K, Kanemura Y, Nonaka M, Asai A, Yokogami K, Takeshima H, Kawahara N, Takayama T, Yao M, Kato M, Nakamura H, Hama N, Sakai R, Ushijima T, Matsutani M, Shibata T, and Nishikawa R
- Subjects
- Central Nervous System Neoplasms pathology, Female, Humans, Male, Neoplasms, Germ Cell and Embryonal therapy, Phosphatidylinositol 3-Kinases genetics, Recurrence, TOR Serine-Threonine Kinases metabolism, Testicular Neoplasms therapy, Central Nervous System Neoplasms genetics, Mutation genetics, Neoplasms, Germ Cell and Embryonal genetics, TOR Serine-Threonine Kinases genetics, Testicular Neoplasms genetics
- Abstract
Germ cell tumors constitute a heterogeneous group that displays a broad spectrum of morphology. They often arise in testes; however, extragonadal occurrence, in particular brain, is not uncommon, and whether they share a common pathogenesis is unknown. We performed whole exome sequencing in 41 pairs of central nervous system germ cell tumors (CNS GCTs) of various histology and their matched normal tissues. We then performed targeted sequencing of 41 selected genes in a total of 124 CNS GCTs, 65 testicular germ cell tumors (tGCTs) and 8 metastatic GCTs to the CNS. The results showed that mutually exclusive mutations of genes involved in the MAPK pathway were most common (48.4 %), typically in KIT (27.4 %), followed by those in the PI3K pathway (12.9 %), particularly in MTOR (6.5 %), among the 124 CNS GCTs. Pure germinomas and non-germinomatous germ cell tumors (NGGCTs), as well as CNS and testicular GCTs, showed similar mutational profiles, suggesting that GCTs share a common molecular pathogenesis. Mutated MTOR identified in CNS GCTs upregulated phosphorylation of the AKT pathway proteins including AKT and 4EBP1 in nutrient-deprived conditions and enhanced soft-agar colony formation; both events were suppressed in a dose-dependent manner by addition of the MTOR inhibitor pp242. Our findings indicate that the dominant genetic drivers of GCTs regardless of the site of origin are activation of the MAPK and/or PI3K pathways by somatic point mutations. Mutated MTOR represents a potential target for novel targeted therapies for refractory GCTs.
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- 2016
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32. Erratum: Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer.
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Fujimoto A, Furuta M, Totoki Y, Tsunoda T, Kato M, Shiraishi Y, Tanaka H, Taniguchi H, Kawakami Y, Ueno M, Gotoh K, Ariizumi S, Wardell CP, Hayami S, Nakamura T, Aikata H, Arihiro K, Boroevich KA, Abe T, Nakano K, Maejima K, Sasaki-Oku A, Ohsawa A, Shibuya T, Nakamura H, Hama N, Hosoda F, Arai Y, Ohashi S, Urushidate T, Nagae G, Yamamoto S, Ueda H, Tatsuno K, Ojima H, Hiraoka N, Okusaka T, Kubo M, Marubashi S, Yamada T, Hirano S, Yamamoto M, Ohdan H, Shimada K, Ishikawa O, Yamaue H, Chayama K, Miyano S, Aburatani H, Shibata T, and Nakagawa H
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- 2016
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33. Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer.
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Fujimoto A, Furuta M, Totoki Y, Tsunoda T, Kato M, Shiraishi Y, Tanaka H, Taniguchi H, Kawakami Y, Ueno M, Gotoh K, Ariizumi S, Wardell CP, Hayami S, Nakamura T, Aikata H, Arihiro K, Boroevich KA, Abe T, Nakano K, Maejima K, Sasaki-Oku A, Ohsawa A, Shibuya T, Nakamura H, Hama N, Hosoda F, Arai Y, Ohashi S, Urushidate T, Nagae G, Yamamoto S, Ueda H, Tatsuno K, Ojima H, Hiraoka N, Okusaka T, Kubo M, Marubashi S, Yamada T, Hirano S, Yamamoto M, Ohdan H, Shimada K, Ishikawa O, Yamaue H, Chayama K, Miyano S, Aburatani H, Shibata T, and Nakagawa H
- Subjects
- DNA Mutational Analysis, DNA, Neoplasm, Genetic Structures, Humans, Neoplasm Proteins genetics, Prognosis, Regulatory Sequences, Nucleic Acid, Sequence Analysis, DNA, Virus Integration, Genome, Human, Liver Neoplasms genetics, Mutation
- Abstract
Liver cancer, which is most often associated with virus infection, is prevalent worldwide, and its underlying etiology and genomic structure are heterogeneous. Here we provide a whole-genome landscape of somatic alterations in 300 liver cancers from Japanese individuals. Our comprehensive analysis identified point mutations, structural variations (STVs), and virus integrations, in noncoding and coding regions. We discovered mutational signatures related to liver carcinogenesis and recurrently mutated coding and noncoding regions, such as long intergenic noncoding RNA genes (NEAT1 and MALAT1), promoters, CTCF-binding sites, and regulatory regions. STV analysis found a significant association with replication timing and identified known (CDKN2A, CCND1, APC, and TERT) and new (ASH1L, NCOR1, and MACROD2) cancer-related genes that were recurrently affected by STVs, leading to altered expression. These results emphasize the value of whole-genome sequencing analysis in discovering cancer driver mutations and understanding comprehensive molecular profiles of liver cancer, especially with regard to STVs and noncoding mutations.
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- 2016
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34. Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma.
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Yachida S, Wood LD, Suzuki M, Takai E, Totoki Y, Kato M, Luchini C, Arai Y, Nakamura H, Hama N, Elzawahry A, Hosoda F, Shirota T, Morimoto N, Hori K, Funazaki J, Tanaka H, Morizane C, Okusaka T, Nara S, Shimada K, Hiraoka N, Taniguchi H, Higuchi R, Oshima M, Okano K, Hirono S, Mizuma M, Arihiro K, Yamamoto M, Unno M, Yamaue H, Weiss MJ, Wolfgang CL, Furukawa T, Nakagama H, Vogelstein B, Kiyono T, Hruban RH, and Shibata T
- Subjects
- Adult, Aged, Aged, 80 and over, Exome, Female, Humans, Male, Middle Aged, Young Adult, Pancreatic Neoplasms, DNA-Binding Proteins genetics, Pancreatic Neoplasms genetics, Proto-Oncogene Proteins c-ets genetics, Transcription Factors genetics
- Abstract
Ampullary carcinomas are highly malignant neoplasms that can have either intestinal or pancreatobiliary differentiation. To characterize somatic alterations in ampullary carcinomas, we performed whole-exome sequencing and DNA copy-number analysis on 60 ampullary carcinomas resected from clinically well-characterized Japanese and American patients. We next selected 92 genes and performed targeted sequencing to validate significantly mutated genes in an additional 112 cancers. The prevalence of driver gene mutations in carcinomas with the intestinal phenotype is different from those with the pancreatobiliary phenotype. We identified a characteristic significantly mutated driver gene (ELF3) as well as previously known driver genes (TP53, KRAS, APC, and others). Functional studies demonstrated that ELF3 silencing in normal human epithelial cells enhances their motility and invasion., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2016
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35. Genomic spectra of biliary tract cancer.
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Nakamura H, Arai Y, Totoki Y, Shirota T, Elzawahry A, Kato M, Hama N, Hosoda F, Urushidate T, Ohashi S, Hiraoka N, Ojima H, Shimada K, Okusaka T, Kosuge T, Miyagawa S, and Shibata T
- Subjects
- Cyclic AMP-Dependent Protein Kinase Catalytic Subunits genetics, DNA Mutational Analysis, DNA-Binding Proteins genetics, Genetic Association Studies, Genetic Predisposition to Disease, Genomics, Humans, Oncogene Proteins, Fusion genetics, Point Mutation, Prognosis, Proto-Oncogene Proteins c-ets genetics, Receptor, Fibroblast Growth Factor, Type 1 genetics, Receptor, Fibroblast Growth Factor, Type 2 genetics, Transcription Factors genetics, Biliary Tract Neoplasms genetics
- Abstract
The incidence of biliary tract cancer (BTC), including intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma and gallbladder cancer, has increased globally; however, no effective targeted molecular therapies have been approved at the present time. Here we molecularly characterized 260 BTCs and uncovered spectra of genomic alterations that included new potential therapeutic targets. Gradient spectra of mutational signatures with a higher burden of the APOBEC-associated mutation signature were observed in gallbladder cancer and ECC. Thirty-two significantly altered genes, including ELF3, were identified, and nearly 40% of cases harbored targetable genetic alterations. Gene fusions involving FGFR2 and PRKACA or PRKACB preferentially occurred in ICC and ECC, respectively, and the subtype-associated prevalence of actionable growth factor-mediated signals was noteworthy. The subgroup with the poorest prognosis had significant enrichment of hypermutated tumors and a characteristic elevation in the expression of immune checkpoint molecules. Accordingly, immune-modulating therapies might also be potentially promising options for these patients.
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- 2015
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36. Trans-ancestry mutational landscape of hepatocellular carcinoma genomes.
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Totoki Y, Tatsuno K, Covington KR, Ueda H, Creighton CJ, Kato M, Tsuji S, Donehower LA, Slagle BL, Nakamura H, Yamamoto S, Shinbrot E, Hama N, Lehmkuhl M, Hosoda F, Arai Y, Walker K, Dahdouli M, Gotoh K, Nagae G, Gingras MC, Muzny DM, Ojima H, Shimada K, Midorikawa Y, Goss JA, Cotton R, Hayashi A, Shibahara J, Ishikawa S, Guiteau J, Tanaka M, Urushidate T, Ohashi S, Okada N, Doddapaneni H, Wang M, Zhu Y, Dinh H, Okusaka T, Kokudo N, Kosuge T, Takayama T, Fukayama M, Gibbs RA, Wheeler DA, Aburatani H, and Shibata T
- Subjects
- Algorithms, Asian People, Carcinoma, Hepatocellular epidemiology, CpG Islands, DNA Mutational Analysis, Exome, Gene Expression Regulation, Neoplastic, Genome, Viral, Hepacivirus genetics, Hepatitis B virus genetics, Humans, Japan, Liver Neoplasms epidemiology, Models, Statistical, Principal Component Analysis, TOR Serine-Threonine Kinases genetics, Telomerase genetics, United States, White People, Carcinoma, Hepatocellular ethnology, Carcinoma, Hepatocellular genetics, Genome, Human, Liver Neoplasms ethnology, Liver Neoplasms genetics, Mutation
- Abstract
Diverse epidemiological factors are associated with hepatocellular carcinoma (HCC) prevalence in different populations. However, the global landscape of the genetic changes in HCC genomes underpinning different epidemiological and ancestral backgrounds still remains uncharted. Here a collection of data from 503 liver cancer genomes from different populations uncovered 30 candidate driver genes and 11 core pathway modules. Furthermore, a collaboration of two large-scale cancer genome projects comparatively analyzed the trans-ancestry substitution signatures in 608 liver cancer cases and identified unique mutational signatures that predominantly contribute to Asian cases. This work elucidates previously unexplored ancestry-associated mutational processes in HCC development. A combination of hotspot TERT promoter mutation, TERT focal amplification and viral genome integration occurs in more than 68% of cases, implicating TERT as a central and ancestry-independent node of hepatocarcinogenesis. Newly identified alterations in genes encoding metabolic enzymes, chromatin remodelers and a high proportion of mTOR pathway activations offer potential therapeutic and diagnostic opportunities.
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- 2014
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37. Unique mutation portraits and frequent COL2A1 gene alteration in chondrosarcoma.
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Totoki Y, Yoshida A, Hosoda F, Nakamura H, Hama N, Ogura K, Yoshida A, Fujiwara T, Arai Y, Toguchida J, Tsuda H, Miyano S, Kawai A, and Shibata T
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- Activin Receptors, Type II genetics, Adolescent, Adult, Aged, Aged, 80 and over, Female, Fibronectins genetics, Fibronectins metabolism, Humans, Isocitrate Dehydrogenase genetics, Male, Middle Aged, Chondrosarcoma genetics, Collagen Type II genetics, Mutation, Osteochondromatosis genetics, Transcriptome
- Abstract
Chondrosarcoma is the second most frequent malignant bone tumor. However, the etiological background of chondrosarcomagenesis remains largely unknown, along with details on molecular alterations and potential therapeutic targets. Massively parallel paired-end sequencing of whole genomes of 10 primary chondrosarcomas revealed that the process of accumulation of somatic mutations is homogeneous irrespective of the pathological subtype or the presence of IDH1 mutations, is unique among a range of cancer types, and shares significant commonalities with that of prostate cancer. Clusters of structural alterations localized within a single chromosome were observed in four cases. Combined with targeted resequencing of additional cartilaginous tumor cohorts, we identified somatic alterations of the COL2A1 gene, which encodes an essential extracellular matrix protein in chondroskeletal development, in 19.3% of chondrosarcoma and 31.7% of enchondroma cases. Epigenetic regulators (IDH1 and YEATS2) and an activin/BMP signal component (ACVR2A) were recurrently altered. Furthermore, a novel FN1-ACVR2A fusion transcript was observed in both chondrosarcoma and osteochondromatosis cases. With the characteristic accumulative process of somatic changes as a background, molecular defects in chondrogenesis and aberrant epigenetic control are primarily causative of both benign and malignant cartilaginous tumors., (© 2014 Totoki et al.; Published by Cold Spring Harbor Laboratory Press.)
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- 2014
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38. Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma.
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Arai Y, Totoki Y, Hosoda F, Shirota T, Hama N, Nakamura H, Ojima H, Furuta K, Shimada K, Okusaka T, Kosuge T, and Shibata T
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- Adenosylhomocysteinase metabolism, Aged, Animals, Bile Duct Neoplasms pathology, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Cholangiocarcinoma pathology, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Female, Humans, In Vitro Techniques, Liver Neoplasms metabolism, Liver Neoplasms pathology, Male, Mice, Mice, Nude, Middle Aged, Molecular Sequence Data, NIH 3T3 Cells, Phenylurea Compounds pharmacology, Pyrimidines pharmacology, RNA-Binding Proteins metabolism, Receptors, Fibroblast Growth Factor antagonists & inhibitors, Receptors, Fibroblast Growth Factor drug effects, Stomach Neoplasms metabolism, Stomach Neoplasms pathology, Bile Duct Neoplasms classification, Bile Duct Neoplasms metabolism, Bile Ducts, Intrahepatic, Cholangiocarcinoma classification, Cholangiocarcinoma metabolism, Receptor, Fibroblast Growth Factor, Type 2 metabolism, Transcriptome
- Abstract
Unlabelled: Cholangiocarcinoma is an intractable cancer, with limited therapeutic options, in which the molecular mechanisms underlying tumor development remain poorly understood. Identification of a novel driver oncogene and applying it to targeted therapies for molecularly defined cancers might lead to improvements in the outcome of patients. We performed massively parallel whole transcriptome sequencing in eight specimens from cholangiocarcinoma patients without KRAS/BRAF/ROS1 alterations and identified two fusion kinase genes, FGFR2-AHCYL1 and FGFR2-BICC1. In reverse-transcriptase polymerase chain reaction (RT-PCR) screening, the FGFR2 fusion was detected in nine patients with cholangiocarcinoma (9/102), exclusively in the intrahepatic subtype (9/66, 13.6%), rarely in colorectal (1/149) and hepatocellular carcinoma (1/96), and none in gastric cancer (0/212). The rearrangements were mutually exclusive with KRAS/BRAF mutations. Expression of the fusion kinases in NIH3T3 cells activated MAPK and conferred anchorage-independent growth and in vivo tumorigenesis of subcutaneous transplanted cells in immune-compromised mice. This transforming ability was attributable to its kinase activity. Treatment with the fibroblast growth factor receptor (FGFR) kinase inhibitors BGJ398 and PD173074 effectively suppressed transformation., Conclusion: FGFR2 fusions occur in 13.6% of intrahepatic cholangiocarcinoma. The expression pattern of these fusions in association with sensitivity to FGFR inhibitors warrant a new molecular classification of cholangiocarcinoma and suggest a new therapeutic approach to the disease., (© 2014 by the American Association for the Study of Liver Diseases.)
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- 2014
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39. Signatures of mutational processes in human cancer.
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Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Børresen-Dale AL, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjörd JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinski M, Jäger N, Jones DT, Jones D, Knappskog S, Kool M, Lakhani SR, López-Otín C, Martin S, Munshi NC, Nakamura H, Northcott PA, Pajic M, Papaemmanuil E, Paradiso A, Pearson JV, Puente XS, Raine K, Ramakrishna M, Richardson AL, Richter J, Rosenstiel P, Schlesner M, Schumacher TN, Span PN, Teague JW, Totoki Y, Tutt AN, Valdés-Mas R, van Buuren MM, van 't Veer L, Vincent-Salomon A, Waddell N, Yates LR, Zucman-Rossi J, Futreal PA, McDermott U, Lichter P, Meyerson M, Grimmond SM, Siebert R, Campo E, Shibata T, Pfister SM, Campbell PJ, and Stratton MR
- Subjects
- Aging genetics, Algorithms, Cell Transformation, Neoplastic pathology, Cytidine Deaminase genetics, DNA genetics, DNA metabolism, DNA Mutational Analysis, Humans, Models, Genetic, Mutagenesis, Insertional genetics, Mutagens pharmacology, Neoplasms enzymology, Neoplasms pathology, Organ Specificity, Reproducibility of Results, Sequence Deletion genetics, Transcription, Genetic genetics, Cell Transformation, Neoplastic genetics, Mutagenesis genetics, Mutation genetics, Neoplasms genetics
- Abstract
All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
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- 2013
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40. Regulatory nexus of synthesis and degradation deciphers cellular Nrf2 expression levels.
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Suzuki T, Shibata T, Takaya K, Shiraishi K, Kohno T, Kunitoh H, Tsuta K, Furuta K, Goto K, Hosoda F, Sakamoto H, Motohashi H, and Yamamoto M
- Subjects
- Animals, Cells, Cultured, ErbB Receptors genetics, Gene Expression, Genetic Predisposition to Disease, Humans, Kelch-Like ECH-Associated Protein 1, Lung Neoplasms metabolism, Macrophages, Mice, Mice, Inbred C57BL, Mice, Inbred ICR, Mice, Knockout, Mutation, Oxidative Stress, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins p21(ras), RNA, Messenger biosynthesis, Risk, Smoking, Transcription, Genetic, Ubiquitination, ras Proteins genetics, Intracellular Signaling Peptides and Proteins metabolism, Lung Neoplasms genetics, NF-E2-Related Factor 2 genetics
- Abstract
Transcription factor Nrf2 (NF-E2-related factor 2) is essential for oxidative and electrophilic stress responses. While it has been well characterized that Nrf2 activity is tightly regulated at the protein level through proteasomal degradation via Keap1 (Kelch-like ECH-associated protein 1)-mediated ubiquitination, not much attention has been paid to the supply side of Nrf2, especially regulation of Nrf2 gene transcription. Here we report that manipulation of Nrf2 transcription is effective in changing the final Nrf2 protein level and activity of cellular defense against oxidative stress even in the presence of Keap1 and under efficient Nrf2 degradation, determined using genetically engineered mouse models. In excellent agreement with this finding, we found that minor A/A homozygotes of a single nucleotide polymorphism (SNP) in the human NRF2 upstream promoter region (rs6721961) exhibited significantly diminished NRF2 gene expression and, consequently, an increased risk of lung cancer, especially those who had ever smoked. Our results support the notion that in addition to control over proteasomal degradation and derepression from degradation/repression, the transcriptional level of the Nrf2 gene acts as another important regulatory point to define cellular Nrf2 levels. These results thus verify the critical importance of human SNPs that influence the levels of transcription of the NRF2 gene for future personalized medicine.
- Published
- 2013
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41. Mouse model for ROS1-rearranged lung cancer.
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Arai Y, Totoki Y, Takahashi H, Nakamura H, Hama N, Kohno T, Tsuta K, Yoshida A, Asamura H, Mutoh M, Hosoda F, Tsuda H, and Shibata T
- Subjects
- Adenocarcinoma drug therapy, Adenocarcinoma pathology, Animals, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Crizotinib, Disease Models, Animal, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Mice, Mice, Nude, Mice, Transgenic, Oncogene Fusion drug effects, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Pyrazoles pharmacology, Pyrazoles therapeutic use, Pyridines pharmacology, Pyridines therapeutic use, Adenocarcinoma genetics, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms genetics, Oncogene Proteins, Fusion genetics, Proto-Oncogene Proteins genetics, Receptor Protein-Tyrosine Kinases genetics
- Abstract
Genetic rearrangement of the ROS1 receptor tyrosine kinase was recently identified as a distinct molecular signature for human non-small cell lung cancer (NSCLC). However, direct evidence of lung carcinogenesis induced by ROS1 fusion genes remains to be verified. The present study shows that EZR-ROS1 plays an essential role in the oncogenesis of NSCLC harboring the fusion gene. EZR-ROS1 was identified in four female patients of lung adenocarcinoma. Three of them were never smokers. Interstitial deletion of 6q22-q25 resulted in gene fusion. Expression of the fusion kinase in NIH3T3 cells induced anchorage-independent growth in vitro, and subcutaneous tumors in nude mice. This transforming ability was attributable to its kinase activity. The ALK/MET/ROS1 kinase inhibitor, crizotinib, suppressed fusion-induced anchorage-independent growth of NIH3T3 cells. Most importantly, established transgenic mouse lines specifically expressing EZR-ROS1 in lung alveolar epithelial cells developed multiple adenocarcinoma nodules in both lungs at an early age. These data suggest that the EZR-ROS1 is a pivotal oncogene in human NSCLC, and that this animal model could be valuable for exploring therapeutic agents against ROS1-rearranged lung cancer.
- Published
- 2013
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42. Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators.
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Fujimoto A, Totoki Y, Abe T, Boroevich KA, Hosoda F, Nguyen HH, Aoki M, Hosono N, Kubo M, Miya F, Arai Y, Takahashi H, Shirakihara T, Nagasaki M, Shibuya T, Nakano K, Watanabe-Makino K, Tanaka H, Nakamura H, Kusuda J, Ojima H, Shimada K, Okusaka T, Ueno M, Shigekawa Y, Kawakami Y, Arihiro K, Ohdan H, Gotoh K, Ishikawa O, Ariizumi S, Yamamoto M, Yamada T, Chayama K, Kosuge T, Yamaue H, Kamatani N, Miyano S, Nakagama H, Nakamura Y, Tsunoda T, Shibata T, and Nakagawa H
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular virology, Female, Genome, Viral genetics, Hepatitis B genetics, Hepatitis B virus genetics, Hepatitis C genetics, Humans, Liver Neoplasms pathology, Liver Neoplasms virology, Male, Middle Aged, Telomerase genetics, Virus Integration genetics, Carcinoma, Hepatocellular genetics, Chromatin genetics, Liver Neoplasms genetics, Mutation
- Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. We sequenced and analyzed the whole genomes of 27 HCCs, 25 of which were associated with hepatitis B or C virus infections, including two sets of multicentric tumors. Although no common somatic mutations were identified in the multicentric tumor pairs, their whole-genome substitution patterns were similar, suggesting that these tumors developed from independent mutations, although their shared etiological backgrounds may have strongly influenced their somatic mutation patterns. Statistical and functional analyses yielded a list of recurrently mutated genes. Multiple chromatin regulators, including ARID1A, ARID1B, ARID2, MLL and MLL3, were mutated in ∼50% of the tumors. Hepatitis B virus genome integration in the TERT locus was frequently observed in a high clonal proportion. Our whole-genome sequencing analysis of HCCs identified the influence of etiological background on somatic mutation patterns and subsequent carcinogenesis, as well as recurrent mutations in chromatin regulators in HCCs.
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- 2012
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43. High-resolution characterization of a hepatocellular carcinoma genome.
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Totoki Y, Tatsuno K, Yamamoto S, Arai Y, Hosoda F, Ishikawa S, Tsutsumi S, Sonoda K, Totsuka H, Shirakihara T, Sakamoto H, Wang L, Ojima H, Shimada K, Kosuge T, Okusaka T, Kato K, Kusuda J, Yoshida T, Aburatani H, and Shibata T
- Subjects
- Carcinoma, Hepatocellular virology, Exons, Gene Rearrangement, Genes, Tumor Suppressor, Genetic Variation, Genomic Library, Genomics, Hepacivirus pathogenicity, Humans, INDEL Mutation, Liver Neoplasms virology, Mutation, Oncogenes, Polymorphism, Single Nucleotide, Selection, Genetic, Carcinoma, Hepatocellular genetics, Liver Neoplasms genetics
- Abstract
Hepatocellular carcinoma, one of the most common virus-associated cancers, is the third most frequent cause of cancer-related death worldwide. By massively parallel sequencing of a primary hepatitis C virus-positive hepatocellular carcinoma (36× coverage) and matched lymphocytes (>28× coverage) from the same individual, we identified more than 11,000 somatic substitutions of the tumor genome that showed predominance of T>C/A>G transition and a decrease of the T>C substitution on the transcribed strand, suggesting preferential DNA repair. Gene annotation enrichment analysis of 63 validated non-synonymous substitutions revealed enrichment of phosphoproteins. We further validated 22 chromosomal rearrangements, generating four fusion transcripts that had altered transcriptional regulation (BCORL1-ELF4) or promoter activity. Whole-exome sequencing at a higher sequence depth (>76× coverage) revealed a TSC1 nonsense substitution in a subpopulation of the tumor cells. This first high-resolution characterization of a virus-associated cancer genome identified previously uncharacterized mutation patterns, intra-chromosomal rearrangements and fusion genes, as well as genetic heterogeneity within the tumor.
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- 2011
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44. Copy number alterations in urothelial carcinomas: their clinicopathological significance and correlation with DNA methylation alterations.
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Nishiyama N, Arai E, Nagashio R, Fujimoto H, Hosoda F, Shibata T, Tsukamoto T, Yokoi S, Imoto I, Inazawa J, and Kanai Y
- Subjects
- Aged, Aged, 80 and over, Comparative Genomic Hybridization, Female, Humans, In Situ Hybridization, Fluorescence, Male, Middle Aged, Multigene Family, Urinary Bladder Neoplasms pathology, DNA Methylation, Gene Dosage, Urinary Bladder Neoplasms genetics
- Abstract
The aim of this study was to clarify the genetic backgrounds underlying the clinicopathological characteristics of urothelial carcinomas (UCs). Array comparative genomic hybridization analysis using a 244K oligonucleotide array was performed on 49 samples of UC tissue. Losses of 2q33.3-q37.3, 4p15.2-q13.1 and 5q13.3-q35.3 and gains of 7p11.2-q11.23 and 20q13.12-q13.2 were correlated with higher histological grade, and gain of 7p21.2-p21.12 was correlated with deeper invasion. Losses of 6q14.1-q27 and 17p13.3-q11.1 and gains of 19q13.12-q13.2 and 20q13.12-q13.33 were correlated with lymph vessel involvement. Loss of 16p12.2-p12.1 and gain of 3q26.32-q29 were correlated with vascular involvement. Losses of 5q14.1-q23.1, 6q14.1-q27, 8p22-p21.3, 11q13.5-q14.1 and 15q11.2-q22.2 and gains of 7p11.2-q11.22 and 19q13.12-q13.2 were correlated with the development of aggressive non-papillary UCs. Losses of 1p32.2-p31.3, 10q11.23-q21.1 and 15q21.3 were correlated with tumor recurrence. Unsupervised hierarchical clustering analysis based on copy number alterations clustered UCs into three subclasses: copy number alterations associated with genome-wide DNA hypomethylation, regional DNA hypermethylation on C-type CpG islands and genome-wide DNA hypo- and hypermethylation were accumulated in clusters A, B(1) and B(2), respectively. Tumor-related genes that may encode therapeutic targets and/or indicators useful for the diagnosis and prognostication of UCs should be explored in the above regions. Both genetic and epigenetic events appear to accumulate during urothelial carcinogenesis, reflecting the clinicopathological diversity of UCs.
- Published
- 2011
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45. Diagnosis and prognostication of ductal adenocarcinomas of the pancreas based on genome-wide DNA methylation profiling by bacterial artificial chromosome array-based methylated CpG island amplification.
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Gotoh M, Arai E, Wakai-Ushijima S, Hiraoka N, Kosuge T, Hosoda F, Shibata T, Kondo T, Yokoi S, Imoto I, Inazawa J, and Kanai Y
- Subjects
- Adult, Aged, Aged, 80 and over, Chromosomes, Artificial, Bacterial, Cohort Studies, Female, Gene Amplification, Genome-Wide Association Study, Humans, Male, Middle Aged, Multivariate Analysis, Oligonucleotide Array Sequence Analysis methods, Polymerase Chain Reaction, Prognosis, Reproducibility of Results, Sensitivity and Specificity, Carcinoma, Pancreatic Ductal diagnosis, Carcinoma, Pancreatic Ductal genetics, CpG Islands, DNA Methylation, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms genetics
- Abstract
To establish diagnostic criteria for ductal adenocarcinomas of the pancreas (PCs), bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed using 139 tissue samples. Twelve BAC clones, for which DNA methylation status was able to discriminate cancerous tissue (T) from noncancerous pancreatic tissue in the learning cohort with a specificity of 100%, were identified. Using criteria that combined the 12 BAC clones, T-samples were diagnosed as cancers with 100% sensitivity and specificity in both the learning and validation cohorts. DNA methylation status on 11 of the BAC clones, which was able to discriminate patients showing early relapse from those with no relapse in the learning cohort with 100% specificity, was correlated with the recurrence-free and overall survival rates in the validation cohort and was an independent prognostic factor by multivariate analysis. Genome-wide DNA methylation profiling may provide optimal diagnostic markers and prognostic indicators for patients with PCs.
- Published
- 2011
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46. Genome-wide DNA methylation profiles in renal tumors of various histological subtypes and non-tumorous renal tissues.
- Author
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Arai E, Wakai-Ushijima S, Fujimoto H, Hosoda F, Shibata T, Kondo T, Yokoi S, Imoto I, Inazawa J, Hirohashi S, and Kanai Y
- Subjects
- Adenoma, Oxyphilic genetics, Adenoma, Oxyphilic pathology, Carcinoma, Renal Cell pathology, Chromosomes, Artificial, Bacterial genetics, Cluster Analysis, Female, Genome-Wide Association Study, Humans, Kidney Neoplasms pathology, Male, Nephrectomy, Oligonucleotide Array Sequence Analysis, Precancerous Conditions genetics, Precancerous Conditions pathology, Tissue Array Analysis, Carcinoma, Renal Cell genetics, DNA Methylation, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic genetics, Kidney Neoplasms genetics
- Abstract
Objective: The aim of this study is to clarify genome-wide DNA methylation profiles in renal tumors of various histological subtypes., Methods: Bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed using tissue samples of 17 patients with papillary renal cell carcinomas (RCCs), chromophobe RCCs and oncocytomas, and the results were compared with those from 51 patients with clear cell RCCs., Results: Unsupervised hierarchical clustering analysis based on DNA methylation status clustered type 1 and type 2 papillary RCCs into different subclasses. Although chromophobe RCCs and oncocytomas were clustered into the same subclass, the DNA methylation status of 21 BAC clones was able to discriminate chromophobe RCCs from oncocytomas. The number of BAC clones showing DNA methylation alteration in non-tumorous renal tissue from patients with chromophobe RCCs and oncocytomas was smaller than that from patients with clear cell RCCs. Biphasic accumulation of DNA methylation alterations was observed in non-tumorous renal tissue from all 68 patients, and patients showing such alterations on more BAC clones had a poorer outcome than patients showing them on fewer BAC clones., Conclusions: DNA methylation profiles determining the histological subtypes of renal tumors developing in individual patients and/or patient outcome may be already established in non-tumorous renal tissue at the precancerous stage., (Copyright © 2011 S. Karger AG, Basel.)
- Published
- 2011
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47. Genome-wide DNA methylation profiles in urothelial carcinomas and urothelia at the precancerous stage.
- Author
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Nishiyama N, Arai E, Chihara Y, Fujimoto H, Hosoda F, Shibata T, Kondo T, Tsukamoto T, Yokoi S, Imoto I, Inazawa J, Hirohashi S, and Kanai Y
- Subjects
- Aged, Aged, 80 and over, Chromosomes, Artificial, Bacterial, CpG Islands, Female, Humans, Male, Middle Aged, Precancerous Conditions pathology, Urinary Bladder Neoplasms pathology, DNA Methylation, Precancerous Conditions genetics, Urinary Bladder Neoplasms genetics
- Abstract
To clarify genome-wide DNA methylation profiles during multistage urothelial carcinogenesis, bacterial artificial chromosome (BAC) array-based methylated CpG island amplification (BAMCA) was performed in 18 normal urothelia obtained from patients without urothelial carcinomas (UCs) (C), 17 noncancerous urothelia obtained from patients with UCs (N), and 40 UCs. DNA hypo- and hypermethylation on multiple BAC clones was observed even in N compared to C. Principal component analysis revealed progressive DNA methylation alterations from C to N, and to UCs. DNA methylation profiles in N obtained from patients with invasive UCs were inherited by the invasive UCs themselves, that is DNA methylation alterations in N were correlated with the development of more malignant UCs. The combination of DNA methylation status on 83 BAC clones selected by Wilcoxon test was able to completely discriminate N from C, and diagnose N as having a high risk of carcinogenesis, with 100% sensitivity and specificity. The combination of DNA methylation status on 20 BAC clones selected by Wilcoxon test was able to completely discriminate patients who suffered from recurrence after surgery from patients who did not. The combination of DNA methylation status for 11 BAC clones selected by Wilcoxon test was able to completely discriminate patients with UCs of the renal pelvis or ureter who suffered from intravesical metachronous UC development from patients who did not. Genome-wide alterations of DNA methylation may participate in urothelial carcinogenesis from the precancerous stage to UC, and DNA methylation profiling may provide optimal indicators for carcinogenetic risk estimation and prognostication.
- Published
- 2010
- Full Text
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48. Genome-wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma.
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Arai E, Ushijima S, Gotoh M, Ojima H, Kosuge T, Hosoda F, Shibata T, Kondo T, Yokoi S, Imoto I, Inazawa J, Hirohashi S, and Kanai Y
- Subjects
- Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular metabolism, Cell Transformation, Neoplastic, Chromosomes, Artificial, Bacterial, CpG Islands, Female, Gene Expression Regulation, Neoplastic, Genome, Human, Humans, Liver metabolism, Liver pathology, Liver Neoplasms diagnosis, Liver Neoplasms metabolism, Male, Middle Aged, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local metabolism, Precancerous Conditions diagnosis, Precancerous Conditions metabolism, Prognosis, Carcinoma, Hepatocellular genetics, DNA Methylation, DNA, Neoplasm genetics, Genome-Wide Association Study, Liver Neoplasms genetics, Neoplasm Recurrence, Local genetics, Precancerous Conditions genetics
- Abstract
To clarify genome-wide DNA methylation profiles during hepatocarcinogenesis, bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed on 126 tissue samples. The average numbers of BAC clones showing DNA hypo- or hypermethylation increased from noncancerous liver tissue obtained from patients with hepatocellular carcinomas (HCCs) (N) to HCCs. N appeared to be at the precancerous stage, showing DNA methylation alterations that were correlated with the future development of HCC. Using Wilcoxon test, 25 BAC clones, whose DNA methylation status was inherited by HCCs from N and were able to discriminate 15 N samples from 10 samples of normal liver tissue obtained from patients without HCCs (C) with 100% sensitivity and specificity, were identified. The criteria using the 25 BAC clones were able to discriminate 24 additional N samples from 26 C samples in the validation set with 95.8% sensitivity and 96.2% specificity. Using Wilcoxon test, 41 BAC clones, whose DNA methylation status was able to discriminate patients who survived more than 4 years after hepatectomy from patients who suffered recurrence within 6 months and died within a year after hepatectomy, were identified. The DNA methylation status of the 41 BAC clones was correlated with the cancer-free and overall survival rates of patients with HCC. Multivariate analysis revealed that satisfying the criteria using the 41 BAC clones was an independent predictor of overall outcome. Genome-wide alterations of DNA methylation may participate in hepatocarcinogenesis from the precancerous stage, and DNA methylation profiling may provide optimal indicators for carcinogenetic risk estimation and prognostication., (Copyright (c) 2009 UICC.)
- Published
- 2009
- Full Text
- View/download PDF
49. Resequencing and copy number analysis of the human tyrosine kinase gene family in poorly differentiated gastric cancer.
- Author
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Kubo T, Kuroda Y, Shimizu H, Kokubu A, Okada N, Hosoda F, Arai Y, Nakamura Y, Taniguchi H, Yanagihara K, Imoto I, Inazawa J, Hirohashi S, and Shibata T
- Subjects
- Cell Line, Tumor, Exons, Gene Dosage, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Genes, Neoplasm, Humans, Receptor Protein-Tyrosine Kinases genetics, Receptor Tyrosine Kinase-like Orphan Receptors genetics, Receptor, trkC genetics, Sequence Analysis, Stomach Neoplasms enzymology, Stomach Neoplasms pathology, src-Family Kinases genetics, Mutation, Protein-Tyrosine Kinases genetics, Stomach Neoplasms genetics
- Abstract
The tyrosine kinase (TK) family is an important regulator of signaling pathways that control a variety of physiological and pathological conditions, and a substantial proportion of TK genes are genetically altered in cancer. To clarify the somatic mutation profile of TK genes and discover potential targets for gastric cancer (GC) therapy, we undertook a systematic screening of mutations in the kinase domains of all human TK genes (636 exons of 90 genes) in 17 GC cell lines and 52 microdissected primary GCs with poorly differentiated histology. We identified 26 non-synonymous alterations (22 genes in total) that included 11 sequence alterations in cell lines and 15 somatic mutations in primary tumors. Recurrent mutations were found in four genes including a known oncogene (NTRK3), the Src kinase family (LTK and CSK) and a potential Wnt signal activator (ROR2). In addition, we analyzed copy number alterations of all the TK gene loci in the same cohort samples by array-based comparative genomic hybridization analysis and identified 24 high-level amplifications and two homozygous deletions. Both sequence alteration and frequent copy number aberration were detected in two TK genes (HCK and ERBB2), strongly suggesting that they encode potential oncogenes in GC. Our focused and integrated analyses of systemic resequencing and gene copy number have revealed the novel onco-kinome profile of GC and pave the way to a comprehensive understanding of the GC genome.
- Published
- 2009
- Full Text
- View/download PDF
50. Krüppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression.
- Author
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Nakamura Y, Migita T, Hosoda F, Okada N, Gotoh M, Arai Y, Fukushima M, Ohki M, Miyata S, Takeuchi K, Imoto I, Katai H, Yamaguchi T, Inazawa J, Hirohashi S, Ishikawa Y, and Shibata T
- Subjects
- Aged, Animals, Blotting, Western, Cell Movement, Cell Proliferation, Cells, Cultured, Chromosomes, Artificial, Bacterial, Chromosomes, Human, Pair 13 genetics, Comparative Genomic Hybridization, Disease Progression, Female, Gene Amplification, Gene Expression Profiling, Gene Silencing, Genome, Human, Humans, Immunoenzyme Techniques, In Situ Hybridization, Fluorescence, Lasers, Male, Mice, Microdissection, NIH 3T3 Cells, Neoplasm Invasiveness, Neoplasm Staging, Oligonucleotide Array Sequence Analysis, Prognosis, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Small Interfering pharmacology, Reverse Transcriptase Polymerase Chain Reaction, Stomach Neoplasms genetics, Stomach Neoplasms metabolism, Cell Differentiation, Kruppel-Like Transcription Factors physiology, Stomach Neoplasms pathology
- Abstract
Gastric cancer is the second common malignant neoplasia in Japan, and its poorly differentiated form is a deadly disease. To identify novel candidate oncogenes contributing to its genesis, we examined copy-number alterations in 50 primary poorly differentiated gastric cancers using an array-based comparative genomic hybridization (array-CGH). Many genetic changes were identified, including a novel amplification of the 13q22 locus. Several genes are located in this locus, and selective knockdown of one for the Krüppel-like factor 12 (KLF12) induced significant growth-arrest in the HGC27 gastric cancer cell line. Microarray analysis also demonstrated that genes associated with cell proliferation were mostly changed by KLF12 knockdown. To explore the oncogenic function of KLF12, we introduced a full length of human KLF12 cDNA into NIH3T3 and AZ-521 cell lines and found that overexpression significantly enhanced their invasive potential. In clinical samples, KLF12 mRNA in cancer tissue was increased in 11 of 28 cases (39%) when compared with normal gastric epithelium. Clinicopathological analysis further demonstrated a significant correlation between KLF12mRNA levels and tumor size (p = 0.038). These data suggest that the KLF12 gene plays an important role in poorly differentiated gastric cancer progression and is a potential target of therapeutic measures.
- Published
- 2009
- Full Text
- View/download PDF
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