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2. Integrated genomic analyses of ovarian carcinoma

Author

Bell, D, Berchuck, A, Birrer, M, Chien, J, Cramer, DW, Dao, F, Dhir, R, DiSaia, P, Gabra, H, Glenn, P, Godwin, AK, Gross, J, Hartmann, L, Huang, M, Huntsman, DG, Iacocca, M, Imielinski, M, Kalloger, S, Karlan, BY, Levine, DA, Mills, GB, Morrison, C, Mutch, D, Olvera, N, Orsulic, S, Park, K, Petrelli, N, Rabeno, B, Rader, JS, Sikic, BI, Smith-McCune, K, Sood, AK, Bowtell, D, Penny, R, Testa, JR, Chang, K, Creighton, CJ, Dinh, HH, Drummond, JA, Fowler, G, Gunaratne, P, Hawes, AC, Kovar, CL, Lewis, LR, Morgan, MB, Newsham, IF, Santibanez, J, Reid, JG, Trevino, LR, Wu, Y-Q, Wang, M, Muzny, DM, Wheeler, DA, Gibbs, RA, Getz, G, Lawrence, MS, Cibulskis, K, Sivachenko, AY, Sougnez, C, Voet, D, Wilkinson, J, Bloom, T, Ardlie, K, Fennell, T, Baldwin, J, Nichol, R, Fisher, S, Gabriel, S, Lander, ES, Ding, L, Fulton, RS, Koboldt, DC, McLellan, MD, Wylie, T, Walker, J, O’Laughlin, M, Dooling, DJ, Fulton, L, Abbott, R, Dees, ND, Zhang, Q, Kandoth, C, Wendl, M, Schierding, W, Shen, D, Harris, CC, Schmidt, H, Kalicki, J, Delehaunty, KD, Fronick, CC, Demeter, R, Cook, L, Wallis, JW, Lin, L, Magrini, VJ, Hodges, JS, Eldred, JM, Smith, SM, Pohl, CS, and Vandin, F

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Cancer Genomics, Biotechnology, Women's Health, Ovarian Cancer, Cancer, Rare Diseases, Breast Cancer, Genetic Testing, Human Genome, 2.1 Biological and endogenous factors, Aged, Carcinoma, DNA Methylation, Female, Gene Dosage, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genomics, Humans, MicroRNAs, Middle Aged, Mutation, Ovarian Neoplasms, RNA, Messenger, Cancer Genome Atlas Research Network, General Science & Technology
Abstract

A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients' lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.

Published
2011

6. Molecular Epidemiology and Antimicrobial Resistance of Clostridioides difficile in Hospitalized Patients From Mexico

Author

Aguilar-Zamora, E, Weimer, BC, Torres, RC, Gomez-Delgado, A, Ortiz-Olvera, N, Aparicio-Ozores, G, Barbero-Becerra, VJ, Torres, J, Camorlinga-Ponce, M, Aguilar-Zamora, E, Weimer, BC, Torres, RC, Gomez-Delgado, A, Ortiz-Olvera, N, Aparicio-Ozores, G, Barbero-Becerra, VJ, Torres, J, and Camorlinga-Ponce, M

Abstract

Clostridioides difficile is a global public health problem, which is a primary cause of antibiotic-associated diarrhea in humans. The emergence of hypervirulent and antibiotic-resistant strains is associated with the increased incidence and severity of the disease. There are limited studies on genomic characterization of C. difficile in Latin America. We aimed to learn about the molecular epidemiology and antimicrobial resistance in C. difficile strains from adults and children in hospitals of México. We studied 94 C. difficile isolates from seven hospitals in Mexico City from 2014 to 2018. Whole-genome sequencing (WGS) was used to determine the genotype and examine the toxigenic profiles. Susceptibility to antibiotics was determined by E-test. Multilocus sequence typing (MLST) was used to determine allelic profiles. Results identified 20 different sequence types (ST) in the 94 isolates, mostly clade 2 and clade 1. ST1 was predominant in isolates from adult and children. Toxigenic strains comprised 87.2% of the isolates that were combinations of tcdAB and cdtAB (tcdA+/tcdB+/cdtA+/cdtB+, followed by tcdA+/tcdB+/cdtA-/cdtB-, tcdA-/tcdB+/cdtA-/ cdtB-, and tcdA-/tcdB-/cdtA+/cdtB+). Toxin profiles were more diverse in isolates from children. All 94 isolates were susceptible to metronidazole and vancomycin, whereas a considerable number of isolates were resistant to clindamycin, fluroquinolones, rifampicin, meropenem, and linezolid. Multidrug-resistant isolates (≥3 antibiotics) comprised 65% of the isolates. The correlation between resistant genotypes and phenotypes was evaluated by the kappa test. Mutations in rpoB and rpoC showed moderate concordance with resistance to rifampicin and mutations in fusA substantial concordance with fusidic acid resistance. cfrE, a gene recently described in one Mexican isolate, was present in 65% of strains linezolid resistant, all ST1 organisms. WGS is a powerful tool to genotype and characterize virulence and antibiotic susceptibility p

Published
2022

11. Medical Weight Problem Diagnosis and Minority Women’s Desire for Thinness

Author

Olvera N

Subjects
Gerontology, Weight problem, Psychology
Abstract

Background and Objectives: Without appropriate medical weight problem diagnosis, minority women might have inaccurate views of their weight status. It is likely that receiving an obesity diagnosis from a physician will raise women’s awareness of their weight status and increase their desire or intent to control their weight. This study assessed: (1) the unique and combined contribution of medical weight diagnosis to desire to be thinner among minority women with overweight/obesity; (2) to what extent ethnicity/race moderated the relation of medical weight problem diagnosis to desire to be thinner; and 3) ethnic/racial differences in perceived and ideal body size, and body dissatisfaction among minority women. Methods: 366 Hispanic and 111 African American women with a mean age of 43.7 years (SD=15.9 years) completed a self-report health survey and figure rating scale. Results: Only 34.1% women reported having received a medical weight problem diagnosis in the past 12 months. Women with obesity (35.4%) were more likely to have received a medical weight problem diagnosis than women with overweight (11.8%) (p

Published
2021
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16. Intolerance of Uncertainty and DSM-5 PTSD Symptom Severity among Trauma Exposed Latina College Women.

Author

Arbona, Consuelo, Rodriguez, L., Dragomir-Davis, M., Olvera, N., de Dios, M. A., and Cano, M. A.

Subjects
WOUNDS & injuries, MENTAL health, ACCIDENTS, COGNITION disorders, PSYCHOLOGY of college students, AROUSAL (Physiology), PARALYSIS, PSYCHOLOGICAL vulnerability, PSYCHOLOGY of Hispanic Americans, UNCERTAINTY, POST-traumatic stress disorder, SEVERITY of illness index, PSYCHOLOGY of women, INTERPERSONAL relations, SEX crimes, NATURAL disasters, AFFECTIVE disorders, STUDENT attitudes, CLASSIFICATION of mental disorders, ANXIETY, BULLYING, BEREAVEMENT, PSYCHOLOGICAL stress, FACIAL nerve
Abstract

Approximately 56 to 84% of college students report having experienced at least one lifetime traumatic or adverse life event. However, little is known about trauma exposure among Latina college students and the association of cognitive vulnerabilities to Posttraumatic Stress Disorder (PTSD) symptoms among this population. Therefore, the purpose of the study was to: (a) explore the traumatic events experienced by 436 Latina college women, and (b) examine the unique contribution of intolerance of uncertainty (IU) and its two subscales (prospective and inhibitory IU) to PTSD-5 symptom severity among the 263 (76%) trauma-exposed Latina college women in the sample. Most frequently reported trauma events included interpersonal bullying and ridicule, attempted sexual assault, traumatic bereavement, and life-threatening accident or natural disaster. As expected, when controlling for college stress and anxiety sensitivity: (a) IU scores were associated with overall PTSD symptom severity and with two of the four PTSD-5 cluster symptoms, arousal/reactivity, and negative alteration in cognition/mood, and (b) IU was not associated with the PTSD-5 intrusion cluster symptoms' severity. Inconsistent with expectations, IU was not uniquely associated with the avoidance of PTSD-5 cluster symptoms. Paralysis in the face of uncertainty (inhibitory IU) was more strongly related to PTSD symptom severity than concerns regarding anticipated uncertainty (prospective IU). Results suggest that IU is a transdiagnostic cognitive vulnerability that plays a unique role in relation to PTSD symptom severity among trauma exposed Latina college women. Therefore, interventions to ameliorate IU could complement established psychological and pharmacological PTSD treatments with this population. [ABSTRACT FROM AUTHOR]

Published
2022
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17. The fitness landscape of the African salmonella typhimurium ST313 strain D23580 reveals unique properties of the pBT1 plasmid

Author

Canals, R., Chaudhuri, R.R., Steiner, R.E., Owen, S.V., Quinones-Olvera, N., Gordon, M.A., Baym, M., Ibba, M., and Hinton, J.C.D.

Abstract

We have used a transposon insertion sequencing (TIS) approach to establish the fitness landscape of the African Salmonella enterica serovar Typhimurium ST313 strain D23580, to complement our previous comparative genomic and functional transcriptomic studies. We used a genome-wide transposon library with insertions every 10 nucleotides to identify genes required for survival and growth in vitro and during infection of murine macrophages. The analysis revealed genomic regions important for fitness under two in vitro growth conditions. Overall, 724 coding genes were required for optimal growth in LB medium, and 851 coding genes were required for growth in SPI-2-inducing minimal medium. These findings were consistent with the essentiality analyses of other S. Typhimurium ST19 and S. Typhi strains. The global mutagenesis approach also identified 60 sRNAs and 413 intergenic regions required for growth in at least one in vitro growth condition. By infecting murine macrophages with the transposon library, we identified 68 genes that were required for intra-macrophage replication but did not impact fitness in vitro. None of these genes were unique to S. Typhimurium D23580, consistent with a high conservation of gene function between S. Typhimurium ST313 and ST19 and suggesting that novel virulence factors are not involved in the interaction of strain D23580 with murine macrophages. We discovered that transposon insertions rarely occurred in many pBT1 plasmid-encoded genes (36), compared with genes carried by the pSLT-BT virulence plasmid and other bacterial plasmids. The key essential protein encoded by pBT1 is a cysteinyl-tRNA synthetase, and our enzymological analysis revealed that the plasmid-encoded CysRSpBT1 had a lower ability to charge tRNA than the chromosomally-encoded CysRSchr enzyme. The presence of aminoacyl-tRNA synthetases in plasmids from a range of Gram-negative and Gram-positive bacteria suggests that plasmid-encoded essential genes are more common than had been appreciated.

Published
2019

24. Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Author

Lazar, AJ, McLellan, MD, Bailey, MH, Miller, CA, Appelbaum, EL, Cordes, MG, Fronick, CC, Fulton, LA, Fulton, RS, Mardis, ER, Schmidt, HK, Wong, W, Wilson, RK, Yellapantula, V, Radenbaugh, AJ, Hoadley, KA, Hayes, DN, Parker, JS, Wilkerson, MD, Auman, JT, Balu, S, Bodenheimer, T, Hoyle, AP, Jefferys, SR, Jones, CD, Lehmann, K-V, Meng, S, Mieczkowski, PA, Mose, LE, Perou, CM, Roach, J, Senbabaoglu, Y, Shi, Y, Simons, JV, Skelly, T, Soloway, MG, Tan, D, Veluvolu, U, Davis, IJ, Hepperla, AJ, Brohl, AS, Kasaian, K, Mungall, K, Sadeghi, S, Barthel, FP, Verhaak, R, Hu, X, Chibon, F, Cherniack, AD, Shih, J, Beroukhim, R, Meyerson, M, Cibulskis, C, Gabriel, SB, Saksena, G, Schumacher, SE, Gao, Q, Wyczalkowski, M, Bowlby, R, Robertson, AG, Ally, A, Balasundaram, M, Brooks, D, Carlsen, R, Chuah, E, Dhalla, N, Holt, RA, Jones, SJM, Lee, D, Li, I, Ma, Y, Marra, MA, Mayo, M, Moore, RA, Mungall, AJ, Schein, JE, Sipahimalani, P, Tam, A, Thiessen, N, Wong, T, Danilova, L, Cope, L, Baylin, SB, Bootwalla, MS, Lai, PH, Laird, PW, Maglinte, DT, Van Den Berg, DJ, Weisenberger, DJ, Wrangle, J, Drill, E, Shen, R, Iype, L, Reynolds, SM, Shmulevich, I, Yau, C, Armenia, J, Liu, EM, Benz, C, Pastore, A, Sanchez-Vega, F, Schultz, N, Akbani, R, Hegde, AM, Liu, W, Lu, Y, Mills, GB, Weinstein, JN, Roszik, J, Anur, P, Spellman, P, Abeshouse, A, Chen, H-W, Gao, J, Heins, Z, Kundra, R, Larsson, E, Ochoa, A, Sander, C, Socci, N, Zhang, H, Noble, MS, Heiman, DI, Kim, J, Chin, L, Getz, G, Cho, J, Defreitas, T, Frazer, S, Gehlenborg, N, Lawrence, MS, Lin, P, Meier, S, Voet, D, Byers, L, Diao, L, Gay, CM, Wang, J, Newton, Y, Cooper, LAD, Gutman, DA, Lee, S, Nalisnik, M, Bowen, J, Gastier-Foster, JM, Gerken, M, Helsel, C, Hobensack, S, Leraas, KM, Lichtenberg, TM, Ramirez, NC, Wise, L, Zmuda, E, Anderson, ML, Castro, P, Ittmann, M, Gordienko, E, Paklina, O, Setdikova, G, Raut, CP, Karlan, BY, Lester, J, Belyaev, D, Fulidou, V, Potapova, O, Voronina, O, Demetri, GD, Ramalingam, SS, Behera, M, Delman, K, Owonikoko, TK, Sica, GL, Boyd, J, Magliocco, A, Salner, A, Bennett, J, Iacocca, M, Swanson, P, Dottino, P, Kalir, T, Pereira, E, Akeredolu, T, Crain, D, Curley, E, Gardner, J, Mallery, D, Morris, S, Paulauskis, J, Penny, R, Shelton, C, Shelton, T, Thompson, E, Hoon, DB, Parfitt, J, Birrer, M, Karseladze, A, Mariamidze, A, Dao, F, Levine, DA, Olvera, N, Maki, RG, Bartlett, J, Eschbacher, J, Dubina, M, Mozgovoy, E, Fedosenko, K, Manikhas, G, Sekhon, H, Ramirez, N, Ingram, DR, Torres, KE, DiSaia, P, Godwin, AK, Godwin, EM, Kuo, H, Madan, R, Reilly, C, Adebamowo, C, Adebamowo, SN, Bocklage, T, Higgins, K, Martinez, C, Boice, L, Grilley-Olson, JE, Huang, M, Perou, AH, Thorne, LB, Rathmell, WK, Gutmann, DH, Singer, S, Chudamani, S, Liu, J, Lolla, L, Naresh, R, Pihl, T, Sun, Q, Wan, Y, Wu, Y, Felau, I, Zenklusen, JC, Demchok, JA, Ferguson, ML, Hutter, CM, Sofia, HJ, Tarnuzzer, R, Wang, Z, Yang, L, Zhang, JJ, Demicco, EG, Doyle, LA, Hornick, JL, Rubin, BP, de Rijn, MV, Baker, L, Riedel, RF, Ding, L, Ladanyi, M, Novak, JE, Van Tine, BA, Davis, LE, Grilley-Olsen, JE, Pollock, RE, Jones, KB, Martignetti, JA, Tong, P, and Network, CGAR

Subjects
0301 basic medicine, Leiomyosarcoma, Adult, Epigenomics, DNA Copy Number Variations, Genomics, Biology, General Biochemistry, Genetics and Molecular Biology, Undifferentiated Pleomorphic Sarcoma, Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, medicine, Cluster Analysis, Humans, ATRX, Aged, Comparative genomics, Aged, 80 and over, Genome, Human, Sarcoma, Middle Aged, medicine.disease, Synovial sarcoma, 030104 developmental biology, 030220 oncology & carcinogenesis, Immunology, DNA methylation, Mutation, Cancer research, Genome-Wide Association Study
Abstract

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes ( TP53 , ATRX , RB1 ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types.

Published
2017
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26. Molecular characterization of mucinous ovarian cancer

Author

Schlappe, B., primary, Mueller, J.J., additional, Olvera, N., additional, Dao, F., additional, Kandoth, C., additional, Bogomolniy, F., additional, Hussein, Y.R., additional, Taylor, B., additional, Soslow, R.A., additional, and Levine, D.A., additional

Published
2016
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28. Integrated genomic analyses of ovarian carcinoma

Author

Bell, D, Berchuck, A, Birrer, M, Chien, J, Cramer, DW, Dao, F, Dhir, R, DiSaia, P, Gabra, H, Glenn, P, Godwin, AK, Triche, T, Berman, BP, Van den Berg, DJ, Buckley, J, Baylin, SB, Zhang, J, Spellman, PT, Purdom, E, Iacocca, M, Shelton, T, Voet, D, Neuvial, P, Bengtsson, H, Jakkula, LR, Durinck, S, Han, J, Dorton, S, Marr, H, Zhang, H, Choi, YG, Wang, V, Wilkinson, J, Nguyen, H, Wang, NJ, Imielinski, M, Ngai, J, Conboy, JG, Parvin, B, Feiler, HS, Speed, TP, Gray, JW, Wu, CJ, Bloom, T, Levine, DA, Li, L, Socci, ND, Liang, Y, Taylor, BS, Kalloger, S, Schultz, N, Borsu, L, Lash, AE, Brennan, C, Ardlie, K, Viale, A, Shukla, S, Grimm, D, Sander, C, Ladanyi, M, Hoadley, KA, Meng, S, Du, Y, Karlan, BY, Shi, Y, Fennell, T, Cibulskis, K, Lawrence, MS, Meyerson, M, Hatfield, M, Mills, GB, Sivachenko, A, Jing, R, Park, RW, Liu, Y, Park, PJ, Ramos, AH, Noble, M, Chin, L, Carter, H, Kim, D, Morris, S, Winckler, W, Karchin, R, Morrison, C, Baldwin, J, Korkola, JE, Yena, P, Heiser, LM, Getz, G, Cho, RJ, Hu, Z, Gabriel, S, Mutch, D, Cerami, E, Rhodes, P, Olshen, A, Verhaak, RGW, Lander, ES, Reva, B, Antipin, Y, Shen, R, Olvera, N, Mankoo, P, Sheridan, R, Ciriello, G, Sherman, M, Chang, WK, Bernanke, JA, Hayes, DN, Carter, SL, Haussler, D, Orsulic, S, Benz, CC, Paulauskis, J, Stuart, JM, Zhang, N, Benz, SC, Sanborn, JZ, Vaske, CJ, Mermel, CH, Zhu, J, Szeto, C, Scott, GK, Yau, C, Rabeno, B, Ding, L, Park, K, Balu, S, Perou, CM, Saksena, G, Wilkerson, MD, Millis, S, Kahn, A, Turman, YJ, Fulton, RS, Onofrio, RC, Greene, JM, Sfeir, R, Jensen, MA, Chen, J, Whitmore, J, Alonso, S, Jordan, J, Chu, A, Rader, JS, Koboldt, DC, Zang, D, Gross, J, Barker, A, Compton, C, Eley, G, Ferguson, M, Fielding, P, Gerhard, DS, Myles, R, McLellan, MD, Schaefer, C, Helms, EB, Shaw, KRM, Sikic, BI, Vaught, J, Vockley, JB, Good, PJ, Guyer, MS, Ozenberger, B, Wylie, T, Peterson, J, Thomson, E, Smith-McCune, K, Sood, AK, Bowtell, D, Hubbard, D, Penny, R, Testa, JR, Chang, K, Walker, J, Dinh, HH, Drummond, JA, Fowler, G, Zhou, X, Gunaratne, P, Hawes, AC, Kovar, CL, Lewis, LR, Gupta, S, Morgan, MB, O'Laughlin, M, Newsham, IF, Santibanez, J, Reid, JG, Trevino, LR, Wu, J, Wu, Y-Q, Wang, M, Muzny, DM, Wheeler, DA, Gibbs, RA, Crenshaw, A, Sivachenko, AY, Topal, MD, Sougnez, C, Dooling, DJ, Fulton, L, Akbani, R, Abbott, R, Dees, ND, Zhang, Q, Kandoth, C, Wendl, M, Schierding, W, Shen, D, Harris, CC, Baggerly, KA, Schmidt, H, Wilson, RK, Kalicki, J, Delehaunty, KD, Fronick, CC, Demeter, R, Cook, L, Wallis, JW, Lin, L, Magrini, VJ, Yung, WK, Hodges, JS, Protopopov, A, Eldred, JM, Smith, SM, Pohl, CS, Vandin, F, Raphael, BJ, Weinstock, GM, Mardis, R, Kim, TM, Hartmann, L, Perna, I, Xiao, Y, Ren, G, Sathiamoorthy, N, Petrelli, N, Lee, E, Kucherlapati, R, Absher, DM, Huang, M, Waite, L, Sherlock, G, Brooks, JD, Li, JZ, Weinstein, JN, Xu, J, Myers, RM, Laird, PW, Cope, L, Herman, JG, Shen, H, Huntsman, DG, Weisenberger, DJ, Noushmehr, H, Pan, F, Massachusetts Institute of Technology. Department of Biology, Lander, Eric S., and Meyerson, Matthew L.

Subjects
endocrine system diseases, Serous carcinoma, Messenger, Gene Dosage, Cancer Genome Atlas Research Network, GYNECOLOGIC-ONCOLOGY-GROUP, GRADE SEROUS CARCINOMA, 0302 clinical medicine, Ovarian carcinoma, Aged, Carcinoma, DNA Methylation, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, MicroRNAs, Middle Aged, Mutation, Ovarian Neoplasms, RNA, Messenger, Genomics, Multidisciplinary, Genetics, HYBRID SELECTION, 0303 health sciences, female genital diseases and pregnancy complications, 3. Good health, Multidisciplinary Sciences, Serous fluid, BRCA MUTATION CARRIERS, 030220 oncology & carcinogenesis, DNA methylation, PARP inhibitor, Science & Technology - Other Topics, General Science & Technology, Biology, Article, 03 medical and health sciences, CLEAR-CELL CARCINOMA, MD Multidisciplinary, microRNA, HIGH-THROUGHPUT ANNOTATION, medicine, DRIVER MUTATIONS, Gene, 030304 developmental biology, Neoplastic, Science & Technology, MUTANT-CELLS, SOMATIC MUTATIONS, medicine.disease, CANCER STATISTICS, Gene Expression Regulation, Cancer research, RNA, Ovarian cancer
Abstract

A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology., National Institutes of Health (U.S.) (Grant U54HG003067), National Institutes of Health (U.S.) (Grant U54HG003273), National Institutes of Health (U.S.) (Grant U54HG003079), National Institutes of Health (U.S.) (Grant U24CA126543), National Institutes of Health (U.S.) (Grant U24CA126544), National Institutes of Health (U.S.) (Grant U24CA126546), National Institutes of Health (U.S.) (Grant U24CA126551), National Institutes of Health (U.S.) (Grant U24CA126554), National Institutes of Health (U.S.) (Grant U24CA126561), National Institutes of Health (U.S.) (Grant U24CA126563), National Institutes of Health (U.S.) (Grant U24CA143882), National Institutes of Health (U.S.) (Grant U24CA143731), National Institutes of Health (U.S.) (Grant U24CA143835), National Institutes of Health (U.S.) (Grant U24CA143845), National Institutes of Health (U.S.) (Grant U24CA143858), National Institutes of Health (U.S.) (Grant U24CA144025), National Institutes of Health (U.S.) (Grant U24CA143866), National Institutes of Health (U.S.) (Grant U24CA143867), National Institutes of Health (U.S.) (Grant U24CA143848), National Institutes of Health (U.S.) (Grant U24CA143843), National Institutes of Health (U.S.) (Grant R21CA135877)

Published
2010

38. Clinical Nephrology - Lab methods and other markers

Author

Kleophas, W., primary, Bieber, B., additional, Robinson, B., additional, Duttlinger, J., additional, Fliser, D., additional, Lonneman, G., additional, Rump, L., additional, Pisoni, R., additional, Port, F., additional, Reichel, H., additional, Daniela, R., additional, Ciocalteu, A., additional, Checherita, I. A., additional, Peride, I., additional, Spataru, D. M., additional, Niculae, A., additional, Laetitia, K., additional, Amna, K., additional, Laurence, D., additional, Aoumeur, H.-A., additional, Flamant, M., additional, Haymann, J.-P., additional, Letavernier, E., additional, Vidal-Petiot, E., additional, Boffa, J.-J., additional, Vrtovsnik, F., additional, Bianco, F., additional, Pessolano, G., additional, Carraro, M., additional, Panzetta, G. O., additional, Ebert, N., additional, Gaedeke, J., additional, Jakob, O., additional, Kuhlmann, M., additional, Martus, P., additional, Van der Giet, M., additional, Scha  ner, E., additional, Khan, I., additional, Law, Y., additional, Turgutalp, K., additional, Ozhan, O., additional, Gok Oguz, E., additional, Kiykim, A., additional, Donadio, C., additional, Hatmi, Z. N., additional, Mahdavi-Mazdeh, M., additional, Morales, E., additional, Gutierrez-Millet, V., additional, Rojas-Rivera, J., additional, Huerta, A., additional, Gutierrez, E., additional, Gutierrez-Solis, E., additional, Polanco, N., additional, Caro, J., additional, Gonza z, E., additional, Praga, M., additional, Marco Mayayo, M., additional, Valdivielso, J., additional, Marti  z, M., additional, Fernaez Giraez, E., additional, Obrador, G., additional, Olvera, N., additional, Ortiz de la Pe, D., additional, Gutie ez, V., additional, Villa, A., additional, Redal-Baigorri, B., additional, Sombolos, K., additional, Tsakiris, D., additional, Boletis, J., additional, Vlahakos, D., additional, Siamopoulos, K., additional, Vargiemezis, V., additional, Nikolaidis, P., additional, Iatrou, C., additional, Dafnis, E., additional, Argyropoulos, C., additional, Xynos, K., additional, Schock-Kusch, D., additional, Shulhevich, Y., additional, Geraci, S., additional, Hesser, J., additional, Stsepankou, D., additional, Neudecker, S., additional, Koenig, S., additional, Hoecklin, F., additional, Pill, J., additional, Gretz, N., additional, Schweda, F., additional, Schreiber, A., additional, Kudo, K., additional, Konta, T., additional, Choi, S. O., additional, Kim, J. S., additional, Kim, M. K., additional, Yang, J. W., additional, Han, B. G., additional, Delanaye, P., additional, Cavalier, E., additional, Masson, I., additional, Mehdi, M., additional, Nicolas, M., additional, Lambermont, B., additional, Dubois, B., additional, Damas, P., additional, Krzesinski, J.-M., additional, Morel, J., additional, Lautrette, A., additional, Christophe, M., additional, Gagneux-Brunon, A., additional, Anne, F., additional, Fre (C)ric, L., additional, Bevc, S., additional, Ekart, R., additional, Hojs, R., additional, Gorenjak, M., additional, Puklavec, L., additional, Hashimoto, N., additional, Suzuki, A., additional, Mitsumoto, K., additional, Shimizu, M., additional, Niihata, K., additional, Kawabata, A., additional, Sakaguchi, Y., additional, Hayashi, T., additional, Shoji, T., additional, Okada, N., additional, Tsubakihara, Y., additional, Hamano, T., additional, Nakano, C., additional, Fujii, N., additional, Obi, Y., additional, Mikami, S., additional, Inoue, K., additional, Matsui, I., additional, Isaka, Y., additional, Rakugi, H., additional, Edvardsson, V., additional, Siguron, B., additional, Thorsteinsdottir, M., additional, Palsson, R., additional, Matsumoto, J., additional, Miyazaki, N., additional, Murata, I., additional, Yoshida, G., additional, Morishita, K., additional, Ushikoshi, H., additional, Nishigaki, K., additional, Ogura, S., additional, Minatoguchi, S., additional, Werneke, U., additional, Ott, M., additional, Salander-Renberg, E., additional, Taylor, D., additional, Stegmayr, B., additional, Surel, S., additional, Wenzlova, M., additional, Silva Junior, G., additional, Vieira, A. P., additional, Couto Bem, A., additional, Alves, M., additional, Torres, A., additional, Meneses, G., additional, Martins, A., additional, Liborio, A., additional, Daher, E., additional, Gluhovschi, G., additional, Modilca, M., additional, Daminescu, L., additional, Gluhovschi, C., additional, Velciov, S., additional, Petrica, L., additional, Gadalean, F., additional, Balgradean, C., additional, Schmeiser, H. H., additional, Kolesnyk, M., additional, Stepanova, N., additional, Surzhko, L., additional, Stashevska, N., additional, Filiopoulos, V., additional, Hadjiyannakos, D., additional, Arvanitis, D., additional, Panagiotopoulos, K., additional, Vlassopoulos, D., additional, Kaesler, N., additional, Schettgen, T., additional, Magdeleyns, E., additional, Brandenburg, V., additional, Vermeer, C., additional, Floege, J., additional, Kr, T., additional, Randone, O., additional, Ferraresi, M., additional, Aroasio, E., additional, Depascale, A., additional, Scognamiglio, S., additional, Consiglio, V., additional, Piccoli, G. B., additional, Jensen, L. V., additional, Lizakowski, S., additional, Rutkowski, P., additional, Tylicki, L., additional, Renke, M., additional, Sulikowska, B., additional, Donderski, R., additional, Bednarski, R., additional, Heleniak, Z., additional, Przybylska, M., additional, Manitius, J., additional, Rutkowski, B., additional, Bobrova, L., additional, Kozlovskaya, N., additional, Kanayama, K., additional, Hasegawa, M., additional, Kitagawa, F., additional, Ishii, J., additional, Yuzawa, Y., additional, Tanaka, K., additional, Sakai, K., additional, Hara, S., additional, Suzuki, Y., additional, Tanaka, Y., additional, Aikawa, A., additional, Hinoshita, F., additional, Hamano, N., additional, Sasaki, E., additional, Kato, A., additional, Katsuki, T., additional, Katsuma, A., additional, Imai, E., additional, Shibata, M., additional, Tada, M., additional, Shimbo, T., additional, Kikuchi, Y., additional, Oka, S., additional, Muramatsu, T., additional, Yanagisawa, N., additional, Fukutake, K., additional, Yamamoto, Y., additional, Ajisawa, A., additional, Tsuchiya, K., additional, Nitta, K., additional, Ando, M., additional, Liang, X., additional, Wang, P., additional, Liu, Z., additional, Zhao, Z., additional, Luyckx, V., additional, Bowker, S., additional, Miekle, A., additional, Toth, E., additional, Heguilen, R., additional, Malvar, A., additional, Hermes, R., additional, Cohen, L., additional, Muguerza, G., additional, Lococo, B., additional, Bernasconi, A., additional, Loboda, O., additional, Dudar, I., additional, Krot, V., additional, Alekseeva, V., additional, Ichinose, M., additional, Sasagawa, N., additional, Toyama, K., additional, Saito, A., additional, Kayamori, Y., additional, Kang, D., additional, Kim, H. 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M., additional, Salma, E. K., additional, Nisrine, B., additional, Mohamed, Z., additional, Guislaine, M., additional, Mohamed Gharbi, B., additional, Benyounes, R., additional, Sotila, G. G., additional, Sorin, R., additional, Irina Magdalena, D., additional, Roxana, C., additional, Claudia, R., additional, Correa Barcellos, F., additional, Hallal, P. H., additional, Bohlke, M., additional, Boscolo Del Vechio, F., additional, Reges, A., additional, Santos, I., additional, Mielke, G., additional, Fortes, M., additional, Antunez, B., additional, Laganovic, M., additional, Vukovic Lela, I., additional, Karanovic, S., additional, Seric, J., additional, Premuic, V., additional, Fitrek, M., additional, Fodor, L., additional, Meljkovic Vrkic, T., additional, Bansal, V., additional, Hoppensteadt, D., additional, and Fareed, J., additional

Published
2012
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49. WNK1 haplotypes and bevacizumab-induced hypertension

Author

Frey, M. K., primary, Olvera, N., additional, Bogomolniy, F., additional, Dao, F., additional, Borsu, L., additional, Konner, J. A., additional, Rizvi, N. A., additional, Barakat, R. R., additional, Dickler, M. N., additional, and Levine, D. A., additional

Published
2008
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