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280 results on '"van Noesel, Carel J M"'

1. Recurrent CLTC::SYK fusions and CSF1R mutations in juvenile xanthogranuloma of soft tissue

Author

Kemps, Paul G., Baelde, Hans J., Vorderman, Ruben H. P., Stelloo, Ellen, Swennenhuis, Joost F., Szuhai, Karoly, Lamers, Meindert H., Kenkhuis, Boyd, Al-Hussaini, Maysa, Briaire-de Bruijn, Inge H., Lam, Suk Wai, Bovée, Judith V. M. G., Cleven, Arjen H. G., Verdijk, Robert M., van Noesel, Carel J. M., van Dijk, Marijke R., Scheijde-Vermeulen, Marijn A., Bruggink, Annette H., van Laar, Jan A. M., de Vries, Andrica C. H., Tissing, Wim J. E., van den Bos, Cor, von Deimling, Andreas, van Wezel, Tom, van Halteren, Astrid G. S., and Hogendoorn, Pancras C. W.

Published
2024
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2. Real-world experience with targeted therapy in patients with histiocytic neoplasms in the Netherlands and in Belgium

Author

Beckers, Erik, van den Berg, Merlijn, van den Bos, Cor, de Bree, Godelieve, Buddingh, Emmeline, Claeys, Kristl, van Daele, Paul, De Haes, Petra, Demandt, Astrid, van Dorp, Suzanne, Hak, Liesbeth, van Halteren, Astrid, van der Houwen, Tim, Jak, Margot, Kerstens, Jeroen, Kwakernaak, Arjan, van Laar, Jan, Leavis, Helen, Leguit, Roos, van de Loosdrecht, Arjan, Morsink, Linde, Mous, Rogier, van Noesel, Max, Oostvogels, Rimke, Potjewijd, Judith, Plattel, Wouter, Roeloffzen, Wilfried, Rutgers, Abraham, Tonino, Sanne, Tousseyn, Thomas, Verdijk, Rob, Vermaat, Joost, Woei-A-Jin, Sherida, Kemps, Paul G., Woei-A-Jin, F. J. Sherida H., Schöffski, Patrick, Vanden Bempt, Isabelle, Meyer-Wentrup, Friederike A. G., Dors, Natasja, van Eijkelenburg, Natasha K. A., Scheijde-Vermeulen, Marijn A., Jazet, Ingrid M., Limper, Maarten, Verdijk, Robert M., Donker, Marjolein L., de Jonge, Nick A., van Noesel, Carel J. M., Hebeda, Konnie M., Tonino, Sanne H., van Laar, Jan A. M., and van Halteren, Astrid G. S.

Published
2024
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6. Clinicogenomic associations in childhood Langerhans cell histiocytosis: an international cohort study

Author

Kemps, Paul G., Zondag, Timo C. E., Arnardóttir, Helga B., Solleveld-Westerink, Nienke, Borst, Jelske, Steenwijk, Eline C., van Egmond, Demi, Swennenhuis, Joost F., Stelloo, Ellen, Trambusti, Irene, Verdijk, Robert M., van Noesel, Carel J. M., Cleven, Arjen H. G., Scheijde-Vermeulen, Marijn A., Koudijs, Marco J., Krsková, Lenka, Hawkins, Cynthia, Egeler, R. Maarten, Brok, Jesper, von Bahr Greenwood, Tatiana, Svojgr, Karel, Beishuizen, Auke, van Laar, Jan A. M., Pötschger, Ulrike, Hutter, Caroline, Sieni, Elena, Minkov, Milen, Abla, Oussama, van Wezel, Tom, van den Bos, Cor, and van Halteren, Astrid G. S.

Published
2023
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8. Molecular characterization of colorectal cancer related peritoneal metastatic disease

Author

Lenos, Kristiaan J., Bach, Sander, Ferreira Moreno, Leandro, ten Hoorn, Sanne, Sluiter, Nina R., Bootsma, Sanne, Vieira Braga, Felipe A., Nijman, Lisanne E., van den Bosch, Tom, Miedema, Daniel M., van Dijk, Erik, Ylstra, Bauke, Kulicke, Ruth, Davis, Fred P., Stransky, Nicolas, Smolen, Gromoslaw A., Coebergh van den Braak, Robert R. J., IJzermans, Jan N. M., Martens, John W. M., Hallam, Sally, Beggs, Andrew D., Kops, Geert J. P. L., Lansu, Nico, Bastiaenen, Vivian P., Klaver, Charlotte E. L., Lecca, Maria C., El Makrini, Khalid, Elbers, Clara C., Dings, Mark P. G., van Noesel, Carel J. M., Kranenburg, Onno, Medema, Jan Paul, Koster, Jan, Koens, Lianne, Punt, Cornelis J. A., Tanis, Pieter J., de Hingh, Ignace H., Bijlsma, Maarten F., Tuynman, Jurriaan B., and Vermeulen, Louis

Published
2022
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9. Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study

Author

Schurink, Bernadette, Roos, Eva, Radonic, Teodora, Barbe, Ellis, Bouman, Catherine S C, de Boer, Hans H, de Bree, Godelieve J, Bulle, Esther B, Aronica, Eleonora M, Florquin, Sandrine, Fronczek, Judith, Heunks, Leo M A, de Jong, Menno D, Guo, Lihui, du Long, Romy, Lutter, Rene, Molenaar, Pam C G, Neefjes-Borst, E Andra, Niessen, Hans W M, van Noesel, Carel J M, Roelofs, Joris J T H, Snijder, Eric J, Soer, Eline C, Verheij, Joanne, Vlaar, Alexander P J, Vos, Wim, van der Wel, Nicole N, van der Wal, Allard C, van der Valk, Paul, and Bugiani, Marianna

Published
2020
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11. RAG1/2 induces double-stranded DNA breaks at non-Ig loci in the proximity of single sequence repeats in developing B cells

Author

CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, Ochodnicka-Mackovicova, Katarina, Mokry, Michal, Haagmans, Martin, Bradley, Ted E, van Noesel, Carel J M, Guikema, Jeroen E J, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, Ochodnicka-Mackovicova, Katarina, Mokry, Michal, Haagmans, Martin, Bradley, Ted E, van Noesel, Carel J M, and Guikema, Jeroen E J

Published
2024

12. External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium

Author

Pathologie Pathologen staf, Cancer, van der Leest, Paul, Rozendal, Pim, Hinrichs, John, van Noesel, Carel J M, Zwaenepoel, Karen, Deiman, Birgit, Huijsmans, Cornelis J J, van Eijk, Ronald, Speel, Ernst Jan M, van Haastert, Rick J, Ligtenberg, Marjolijn J L, van Schaik, Ron H N, Jansen, Maurice P H M, Dubbink, Hendrikus J, de Leng, Wendy W, Leers, Mathie P G, Tamminga, Menno, van den Broek, Daan, van Kempen, Léon C, Schuuring, Ed, Pathologie Pathologen staf, Cancer, van der Leest, Paul, Rozendal, Pim, Hinrichs, John, van Noesel, Carel J M, Zwaenepoel, Karen, Deiman, Birgit, Huijsmans, Cornelis J J, van Eijk, Ronald, Speel, Ernst Jan M, van Haastert, Rick J, Ligtenberg, Marjolijn J L, van Schaik, Ron H N, Jansen, Maurice P H M, Dubbink, Hendrikus J, de Leng, Wendy W, Leers, Mathie P G, Tamminga, Menno, van den Broek, Daan, van Kempen, Léon C, and Schuuring, Ed

Published
2024

13. External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium

Author

van der Leest, Paul, primary, Rozendal, Pim, additional, Hinrichs, John, additional, van Noesel, Carel J M, additional, Zwaenepoel, Karen, additional, Deiman, Birgit, additional, Huijsmans, Cornelis J J, additional, van Eijk, Ronald, additional, Speel, Ernst Jan M, additional, van Haastert, Rick J, additional, Ligtenberg, Marjolijn J L, additional, van Schaik, Ron H N, additional, Jansen, Maurice P H M, additional, Dubbink, Hendrikus J, additional, de Leng, Wendy W, additional, Leers, Mathie P G, additional, Tamminga, Menno, additional, van den Broek, Daan, additional, van Kempen, Léon C, additional, and Schuuring, Ed, additional

Published
2024
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14. Recommendations for the clinical interpretation and reporting of copy number gains using gene panel NGS analysis in routine diagnostics

Author

Eijkelenboom, Astrid, Tops, Bastiaan B. J., van den Berg, Anke, van den Brule, Adrianus J. C., Dinjens, Winand N. M., Dubbink, Hendrikus J., ter Elst, Arja, Geurts-Giele, Willemina R. R., Groenen, Patricia J. T. A., Groenendijk, Floris H., Heideman, Daniëlle A. M., Huibers, Manon M. H., Huijsmans, Cornelis J. J., Jeuken, Judith W. M., van Kempen, Léon C., Korpershoek, Esther, Kroeze, Leonie I., de Leng, Wendy W. J., van Noesel, Carel J. M., Speel, Ernst-Jan M., Vogel, Maartje J., van Wezel, Tom, Nederlof, Petra M., Schuuring, Ed, and Ligtenberg, Marjolijn J. L.

Published
2019
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15. BRAF V600E is associated with higher incidence of second cancers in adults with Langerhans cell histiocytosis

Author

Acosta-Medina, Aldo A., primary, Kemps, Paul G., additional, Zondag, Timo C. E., additional, Abeykoon, Jithma P., additional, Forma-Borst, Jelske, additional, Steenwijk, Eline C., additional, Feijen, Elizabeth A. M., additional, Teepen, Jop C., additional, Bennani, N. Nora, additional, Schram, Susan M., additional, Shah, Mithun V., additional, Davidge-Pitts, Caroline, additional, Koster, Matthew J., additional, Ryu, Jay H., additional, Vassallo, Robert, additional, Tobin, W. Oliver, additional, Young, Jason R., additional, Dasari, Surendra, additional, Rech, Karen, additional, Ravindran, Aishwarya, additional, Cleven, Arjen H. G., additional, Verdijk, Robert M., additional, van Noesel, Carel J. M., additional, Balgobind, Brian V., additional, Bouma, Gerrit Joan, additional, Saeed, Peerooz, additional, Bramer, Jos A. M., additional, de Groen, Ruben A. L., additional, Vermaat, Joost S. P., additional, van de Sande, Michiel A. J., additional, Smit, Egbert F., additional, Langerak, Anton W., additional, van Wezel, Tom, additional, Tonino, Sanne H., additional, van den Bos, Cor, additional, van Laar, Jan A. M., additional, Go, Ronald S., additional, Goyal, Gaurav, additional, and van Halteren, Astrid G. S., additional

Published
2023
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16. Demographics and additional haematologic cancers of patients with histiocytic/dendritic cell neoplasms.

Author

Kemps, Paul G, Kester, Lennart, Scheijde‐Vermeulen, Marijn A, van Noesel, Carel J M, Verdijk, Robert M, Diepstra, Arjan, van Marion, Ariënne M W, Dors, Natasja, van den Bos, Cor, Bruggink, Annette H, Hogendoorn, Pancras C W, and van Halteren, Astrid G S

Subjects
DEMOGRAPHIC characteristics, DENDRITIC cells, LANGERHANS-cell histiocytosis, CANCER patients, TUMORS, RETICULUM cell sarcoma
Abstract

Aims: The discovery of somatic genetic alterations established many histiocytic disorders as haematologic neoplasms. We aimed to investigate the demographic characteristics and additional haematologic cancers of patients diagnosed with histiocytic disorders in The Netherlands. Methods and results: We retrieved data on histiocytosis patients from the Dutch Nationwide Pathology Databank (Palga). During 1993 to 2022, more than 4000 patients with a pathologist‐assigned diagnosis of a histiocytic disorder were registered in Palga. Xanthogranulomas were the most common subtype, challenging the prevailing assumption that Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder. LCH and juvenile xanthogranuloma (JXG) had a peak incidence in the first years of life; males were overrepresented among all histiocytosis subgroups. 118 patients had a histiocytic disorder and an additional haematologic malignancy, including 107 (91%) adults at the time of histiocytosis diagnosis. In 16/118 patients, both entities had been analysed for the same genetic alteration(s). In 11 of these 16 patients, identical genetic alterations had been detected in both haematologic neoplasms. This included two patients with PAX5 p.P80R mutated B cell acute lymphoblastic leukaemia and secondary histiocytic sarcoma, further supporting that PAX5 alterations may predispose (precursor) B cells to differentiate into the myeloid lineage. All 4/11 patients with myeloid neoplasms as their additional haematologic malignancy had shared N/KRAS mutations. Conclusions: This population‐based study highlights the frequency of xanthogranulomas. Furthermore, our data add to the growing evidence supporting clonal relationships between histiocytic/dendritic cell neoplasms and additional myeloid or lymphoid malignancies. Particularly adult histiocytosis patients should be carefully evaluated for the development of these associated haematologic cancers. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Long-term Survival Update and Extended RAS Mutational Analysis of the CAIRO2 Trial: Addition of Cetuximab to CAPOX/Bevacizumab in Metastatic Colorectal Cancer

Author

MS Medische Oncologie, Cancer, Epi Kanker Team B, Ten Hoorn, Sanne, Mol, Linda, Sommeijer, Dirkje W, Nijman, Lisanne, van den Bosch, Tom, de Back, Tim R, Ylstra, Bauke, van Dijk, Erik, van Noesel, Carel J M, Reinten, Roy J, Nagtegaal, Iris D, Koopman, Miriam, Punt, Cornelis J A, Vermeulen, Louis, MS Medische Oncologie, Cancer, Epi Kanker Team B, Ten Hoorn, Sanne, Mol, Linda, Sommeijer, Dirkje W, Nijman, Lisanne, van den Bosch, Tom, de Back, Tim R, Ylstra, Bauke, van Dijk, Erik, van Noesel, Carel J M, Reinten, Roy J, Nagtegaal, Iris D, Koopman, Miriam, Punt, Cornelis J A, and Vermeulen, Louis

Published
2023

18. BRAFV600E is associated with higher incidence of second cancers in adults with Langerhans cell histiocytosis

Author

Acosta-Medina, Aldo A., Kemps, Paul G., Zondag, Timo C. E., Abeykoon, Jithma P., Forma-Borst, Jelske, Steenwijk, Eline C., Feijen, Elizabeth A. M., Teepen, Jop C., Bennani, N. Nora, Schram, Susan M., Shah, Mithun V., Davidge-Pitts, Caroline, Koster, Matthew J., Ryu, Jay H., Vassallo, Robert, Tobin, W. Oliver, Young, Jason R., Dasari, Surendra, Rech, Karen, Ravindran, Aishwarya, Cleven, Arjen H. G., Verdijk, Robert M., van Noesel, Carel J. M., Balgobind, Brian V., Bouma, Gerrit Joan, Saeed, Peerooz, Bramer, Jos A. M., de Groen, Ruben A. L., Vermaat, Joost S. P., van de Sande, Michiel A. J., Smit, Egbert F., Langerak, Anton W., van Wezel, Tom, Tonino, Sanne H., van den Bos, Cor, van Laar, Jan A. M., Go, Ronald S., Goyal, Gaurav, and van Halteren, Astrid G. S.

Published
2023
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19. Neuroblastoma is composed of two super-enhancer-associated differentiation states

Author

van Groningen, Tim, Koster, Jan, Valentijn, Linda J, Zwijnenburg, Danny A, Akogul, Nurdan, Hasselt, Nancy E, Broekmans, Marloes, Haneveld, Franciska, Nowakowska, Natalia E, Bras, Johannes, van Noesel, Carel J M, Jongejan, Aldo, van Kampen, Antoine H, Koster, Linda, Baas, Frank, van Dijk-Kerkhoven, Lianne, Huizer-Smit, Margriet, Lecca, Maria C, Chan, Alvin, Lakeman, Arjan, Molenaar, Piet, Volckmann, Richard, Westerhout, Ellen M, Hamdi, Mohamed, van Sluis, Peter G, Ebus, Marli E, Molenaar, Jan J, Tytgat, Godelieve A, Westerman, Bart A, van Nes, Johan, and Versteeg, Rogier

Published
2017
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24. DNA Methylation Analysis to predict Regression of high-grade anal Intraepithelial Neoplasia in HIV+ men (MARINE): a cohort study protocol

Author

Dias Gonçalves Lima, Fernando, primary, van der Zee, Ramon P, additional, Dick, Stèfanie, additional, van Noesel, Carel J M, additional, Berkhof, Johannes, additional, Schim van der Loeff, Maarten F, additional, Prins, Jan M, additional, Steenbergen, Renske D M, additional, and de Vries, Henry J C, additional

Published
2022
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25. The earliest events in BRAF-mutant colorectal cancer: exome sequencing of sessile serrated lesions with a tiny focus dysplasia or cancer reveals recurring mutations in two distinct progression pathways

Author

Bleijenberg, Arne G. C., IJspeert, Joep E. G., Mulder, Jos B. G., Drillenburg, Paul, Stel, Herbert V., Lodder, Elisabeth M., Carvalho, Beatriz, Jansen, Jade, Meijer, Gerrit, van Eeden, Susanne, Dekker, Evelien, van Noesel, Carel J. M., Gastroenterology and Hepatology, Human Genetics, ACS - Heart failure & arrhythmias, Experimental Immunology, Graduate School, Pathology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and CCA - Cancer biology and immunology

Subjects
immunocytochemistry, mismatch repair genes, serrated neoplasia pathway, colon, colorectal cancer, microsatellite instability, DNA sequencing, serrated polyps, BRAF
Abstract

Around 15–30% of colorectal cancers (CRC) develop from sessile serrated lesions (SSLs). After many years of indolent growth, SSLs can develop dysplasia and rapidly progress to CRC through events that are only partially understood. We studied molecular events at the very early stages of progression of SSLs via the MLH1-proficient and deficient pathways to CRC. We collected a cohort of rare SSLs with a small focus (

Published
2022

26. Molecular characterization of colorectal cancer related peritoneal metastatic disease

Author

Lenos, Kristiaan J, Bach, Sander, Ferreira Moreno, Leandro, Ten Hoorn, Sanne, Sluiter, Nina R, Bootsma, Sanne, Vieira Braga, Felipe A, Nijman, Lisanne E, van den Bosch, Tom, Miedema, Daniel M, van Dijk, Erik, Ylstra, Bauke, Kulicke, Ruth, Davis, Fred P, Stransky, Nicolas, Smolen, Gromoslaw A, Coebergh van den Braak, Robert R J, IJzermans, Jan N M, Martens, John W M, Hallam, Sally, Beggs, Andrew D, Kops, Geert J P L, Lansu, Nico, Bastiaenen, Vivian P, Klaver, Charlotte E L, Lecca, Maria C, El Makrini, Khalid, Elbers, Clara C, Dings, Mark P G, van Noesel, Carel J M, Kranenburg, Onno, Medema, Jan Paul, Koster, Jan, Koens, Lianne, Punt, Cornelis J A, Tanis, Pieter J, de Hingh, Ignace H, Bijlsma, Maarten F, Tuynman, Jurriaan B, Vermeulen, Louis, Lenos, Kristiaan J, Bach, Sander, Ferreira Moreno, Leandro, Ten Hoorn, Sanne, Sluiter, Nina R, Bootsma, Sanne, Vieira Braga, Felipe A, Nijman, Lisanne E, van den Bosch, Tom, Miedema, Daniel M, van Dijk, Erik, Ylstra, Bauke, Kulicke, Ruth, Davis, Fred P, Stransky, Nicolas, Smolen, Gromoslaw A, Coebergh van den Braak, Robert R J, IJzermans, Jan N M, Martens, John W M, Hallam, Sally, Beggs, Andrew D, Kops, Geert J P L, Lansu, Nico, Bastiaenen, Vivian P, Klaver, Charlotte E L, Lecca, Maria C, El Makrini, Khalid, Elbers, Clara C, Dings, Mark P G, van Noesel, Carel J M, Kranenburg, Onno, Medema, Jan Paul, Koster, Jan, Koens, Lianne, Punt, Cornelis J A, Tanis, Pieter J, de Hingh, Ignace H, Bijlsma, Maarten F, Tuynman, Jurriaan B, and Vermeulen, Louis

Abstract

A significant proportion of colorectal cancer (CRC) patients develop peritoneal metastases (PM) in the course of their disease. PMs are associated with a poor quality of life, significant morbidity and dismal disease outcome. To improve care for this patient group, a better understanding of the molecular characteristics of CRC-PM is required. Here we present a comprehensive molecular characterization of a cohort of 52 patients. This reveals that CRC-PM represent a distinct CRC molecular subtype, CMS4, but can be further divided in three separate categories, each presenting with unique features. We uncover that the CMS4-associated structural protein Moesin plays a key role in peritoneal dissemination. Finally, we define specific evolutionary features of CRC-PM which indicate that polyclonal metastatic seeding underlies these lesions. Together our results suggest that CRC-PM should be perceived as a distinct disease entity.

Published
2022

27. Biological and Clinical Implications of Gene-Expression Profiling in Diffuse Large B-Cell Lymphoma: A Proposal for a Targeted BLYM-777 Consortium Panel as Part of a Multilayered Analytical Approach

Author

Cancer, MS Hematologie, Infection & Immunity, de Groot, Fleur A, de Groen, Ruben A L, van den Berg, Anke, Jansen, Patty M, Lam, King H, Mutsaers, Pim G N J, van Noesel, Carel J M, Chamuleau, Martine E D, Stevens, Wendy B C, Plaça, Jessica R, Mous, Rogier, Kersten, Marie José, van der Poel, Marjolein M W, Tousseyn, Thomas, Woei-A-Jin, F J Sherida H, Diepstra, Arjan, Nijland, Marcel, Vermaat, Joost S P, Cancer, MS Hematologie, Infection & Immunity, de Groot, Fleur A, de Groen, Ruben A L, van den Berg, Anke, Jansen, Patty M, Lam, King H, Mutsaers, Pim G N J, van Noesel, Carel J M, Chamuleau, Martine E D, Stevens, Wendy B C, Plaça, Jessica R, Mous, Rogier, Kersten, Marie José, van der Poel, Marjolein M W, Tousseyn, Thomas, Woei-A-Jin, F J Sherida H, Diepstra, Arjan, Nijland, Marcel, and Vermaat, Joost S P

Published
2022

28. ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

Author

Kemps, Paul G, Picarsic, Jennifer, Durham, Benjamin H, Hélias-Rodzewicz, Zofia, Hiemcke-Jiwa, Laura, van den Bos, Cor, van de Wetering, Marianne D, van Noesel, Carel J M, van Laar, Jan A M, Verdijk, Robert M, Flucke, Uta E, Hogendoorn, Pancras C W, Woei-A-Jin, F J Sherida H, Sciot, Raf, Beilken, Andrea, Feuerhake, Friedrich, Ebinger, Martin, Möhle, Robert, Fend, Falko, Bornemann, Antje, Wiegering, Verena, Ernestus, Karen, Méry, Tina, Gryniewicz-Kwiatkowska, Olga, Dembowska-Baginska, Bozenna, Evseev, Dmitry A, Potapenko, Vsevolod, Baykov, Vadim V, Gaspari, Stefania, Rossi, Sabrina, Gessi, Marco, Tamburrini, Gianpiero, Héritier, Sébastien, Donadieu, Jean, Bonneau-Lagacherie, Jacinthe, Lamaison, Claire, Farnault, Laure, Fraitag, Sylvie, Jullié, Marie-Laure, Haroche, Julien, Collin, Matthew, Allotey, Jackie, Madni, Majid, Turner, Kerry, Picton, Susan, Barbaro, Pasquale M, Poulin, Alysa, Tam, Ingrid S, El Demellawy, Dina, Empringham, Brianna, Whitlock, James A, Raghunathan, Aditya, Swanson, Amy A, Suchi, Mariko, Brandt, Jon M, Yaseen, Nabeel R, Weinstein, Joanna L, Eldem, Irem, Sisk, Bryan A, Sridhar, Vaishnavi, Atkinson, Mandy, Massoth, Lucas R, Hornick, Jason L, Alexandrescu, Sanda, Yeo, Kee Kiat, Petrova-Drus, Kseniya, Peeke, Stephen Z, Muñoz-Arcos, Laura S, Leino, Daniel G, Grier, David D, Lorsbach, Robert, Roy, Somak, Kumar, Ashish R, Garg, Shipra, Tiwari, Nishant, Schafernak, Kristian T, Henry, Michael M, van Halteren, Astrid G S, Abla, Oussama, Diamond, Eli L, Emile, Jean-François, Tamburrini, Gianpiero (ORCID:0000-0002-7139-5711), Kemps, Paul G, Picarsic, Jennifer, Durham, Benjamin H, Hélias-Rodzewicz, Zofia, Hiemcke-Jiwa, Laura, van den Bos, Cor, van de Wetering, Marianne D, van Noesel, Carel J M, van Laar, Jan A M, Verdijk, Robert M, Flucke, Uta E, Hogendoorn, Pancras C W, Woei-A-Jin, F J Sherida H, Sciot, Raf, Beilken, Andrea, Feuerhake, Friedrich, Ebinger, Martin, Möhle, Robert, Fend, Falko, Bornemann, Antje, Wiegering, Verena, Ernestus, Karen, Méry, Tina, Gryniewicz-Kwiatkowska, Olga, Dembowska-Baginska, Bozenna, Evseev, Dmitry A, Potapenko, Vsevolod, Baykov, Vadim V, Gaspari, Stefania, Rossi, Sabrina, Gessi, Marco, Tamburrini, Gianpiero, Héritier, Sébastien, Donadieu, Jean, Bonneau-Lagacherie, Jacinthe, Lamaison, Claire, Farnault, Laure, Fraitag, Sylvie, Jullié, Marie-Laure, Haroche, Julien, Collin, Matthew, Allotey, Jackie, Madni, Majid, Turner, Kerry, Picton, Susan, Barbaro, Pasquale M, Poulin, Alysa, Tam, Ingrid S, El Demellawy, Dina, Empringham, Brianna, Whitlock, James A, Raghunathan, Aditya, Swanson, Amy A, Suchi, Mariko, Brandt, Jon M, Yaseen, Nabeel R, Weinstein, Joanna L, Eldem, Irem, Sisk, Bryan A, Sridhar, Vaishnavi, Atkinson, Mandy, Massoth, Lucas R, Hornick, Jason L, Alexandrescu, Sanda, Yeo, Kee Kiat, Petrova-Drus, Kseniya, Peeke, Stephen Z, Muñoz-Arcos, Laura S, Leino, Daniel G, Grier, David D, Lorsbach, Robert, Roy, Somak, Kumar, Ashish R, Garg, Shipra, Tiwari, Nishant, Schafernak, Kristian T, Henry, Michael M, van Halteren, Astrid G S, Abla, Oussama, Diamond, Eli L, Emile, Jean-François, and Tamburrini, Gianpiero (ORCID:0000-0002-7139-5711)

Abstract

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.

Published
2022

29. BRAFV600Eis associated with higher incidence of second cancers in adults with Langerhans cell histiocytosis

Author

Acosta-Medina, Aldo A., Kemps, Paul G., Zondag, Timo C. E., Abeykoon, Jithma P., Forma-Borst, Jelske, Steenwijk, Eline C., Feijen, Elizabeth A. M., Teepen, Jop C., Bennani, N. Nora, Schram, Susan M., Shah, Mithun V., Davidge-Pitts, Caroline, Koster, Matthew J., Ryu, Jay H., Vassallo, Robert, Tobin, W. Oliver, Young, Jason R., Dasari, Surendra, Rech, Karen, Ravindran, Aishwarya, Cleven, Arjen H. G., Verdijk, Robert M., van Noesel, Carel J. M., Balgobind, Brian V., Bouma, Gerrit Joan, Saeed, Peerooz, Bramer, Jos A. M., de Groen, Ruben A. L., Vermaat, Joost S. P., van de Sande, Michiel A. J., Smit, Egbert F., Langerak, Anton W., van Wezel, Tom, Tonino, Sanne H., van den Bos, Cor, van Laar, Jan A. M., Go, Ronald S., Goyal, Gaurav, and van Halteren, Astrid G. S.

Abstract

[Display omitted]

Published
2023
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30. A large family with MSH3-related polyposis

Author

Aelvoet, Arthur S., primary, Hoekman, Daniël R., additional, Redeker, Bert J. W., additional, Weegenaar, Jitske, additional, Dekker, Evelien, additional, van Noesel, Carel J. M., additional, and Duijkers, Floor A. M., additional

Published
2022
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31. Dutch National Round Robin Trial on Plasma-Derived Circulating Cell-Free DNA Extraction Methods Routinely Used in Clinical Pathology for Molecular Tumor Profiling

Author

van der Leest, Paul, primary, Ketelaar, Emma M, additional, van Noesel, Carel J M, additional, van den Broek, Daan, additional, van Boerdonk, Robert A A, additional, Deiman, Birgit, additional, Rifaela, Naomi, additional, van der Geize, Robert, additional, Huijsmans, Cornelis J J, additional, Speel, Ernst Jan M, additional, Geerlings, Maartje J, additional, van Schaik, Ron H N, additional, Jansen, Maurice P H M, additional, Dane-Vogelaar, Ria, additional, Driehuis, Else, additional, Leers, Mathie P G, additional, Sidorenkov, Grigory, additional, Tamminga, Menno, additional, van Kempen, Léon C, additional, and Schuuring, Ed, additional

Published
2022
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32. Biological and Clinical Implications of Gene-Expression Profiling in Diffuse Large B-Cell Lymphoma: A Proposal for a Targeted BLYM-777 Consortium Panel as Part of a Multilayered Analytical Approach

Author

de Groot, Fleur A., primary, de Groen, Ruben A. L., additional, van den Berg, Anke, additional, Jansen, Patty M., additional, Lam, King H., additional, Mutsaers, Pim G. N. J., additional, van Noesel, Carel J. M., additional, Chamuleau, Martine E. D., additional, Stevens, Wendy B. C., additional, Plaça, Jessica R., additional, Mous, Rogier, additional, Kersten, Marie José, additional, van der Poel, Marjolein M. W., additional, Tousseyn, Thomas, additional, Woei-a-Jin, F. J. Sherida H., additional, Diepstra, Arjan, additional, Nijland, Marcel, additional, and Vermaat, Joost S. P., additional

Published
2022
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33. ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

Author

Kemps, Paul G., primary, Picarsic, Jennifer, additional, Durham, Benjamin H., additional, Hélias-Rodzewicz, Zofia, additional, Hiemcke-Jiwa, Laura, additional, van den Bos, Cor, additional, van de Wetering, Marianne D., additional, van Noesel, Carel J. M., additional, van Laar, Jan A. M., additional, Verdijk, Robert M., additional, Flucke, Uta E., additional, Hogendoorn, Pancras C. W., additional, Woei-A-Jin, F. J. Sherida H., additional, Sciot, Raf, additional, Beilken, Andreas, additional, Feuerhake, Friedrich, additional, Ebinger, Martin, additional, Möhle, Robert, additional, Fend, Falko, additional, Bornemann, Antje, additional, Wiegering, Verena, additional, Ernestus, Karen, additional, Méry, Tina, additional, Gryniewicz-Kwiatkowska, Olga, additional, Dembowska-Baginska, Bozenna, additional, Evseev, Dmitry A., additional, Potapenko, Vsevolod, additional, Baykov, Vadim V., additional, Gaspari, Stefania, additional, Rossi, Sabrina, additional, Gessi, Marco, additional, Tamburrini, Gianpiero, additional, Héritier, Sébastien, additional, Donadieu, Jean, additional, Bonneau-Lagacherie, Jacinthe, additional, Lamaison, Claire, additional, Farnault, Laure, additional, Fraitag, Sylvie, additional, Jullié, Marie-Laure, additional, Haroche, Julien, additional, Collin, Matthew, additional, Allotey, Jackie, additional, Madni, Majid, additional, Turner, Kerry, additional, Picton, Susan, additional, Barbaro, Pasquale M., additional, Poulin, Alysa, additional, Tam, Ingrid S., additional, El Demellawy, Dina, additional, Empringham, Brianna, additional, Whitlock, James A., additional, Raghunathan, Aditya, additional, Swanson, Amy A., additional, Suchi, Mariko, additional, Brandt, Jon M., additional, Yaseen, Nabeel R., additional, Weinstein, Joanna L., additional, Eldem, Irem, additional, Sisk, Bryan A., additional, Sridhar, Vaishnavi, additional, Atkinson, Mandy, additional, Massoth, Lucas R., additional, Hornick, Jason L., additional, Alexandrescu, Sanda, additional, Yeo, Kee Kiat, additional, Petrova-Drus, Kseniya, additional, Peeke, Stephen Z., additional, Muñoz-Arcos, Laura S., additional, Leino, Daniel G., additional, Grier, David D., additional, Lorsbach, Robert, additional, Roy, Somak, additional, Kumar, Ashish R., additional, Garg, Shipra, additional, Tiwari, Nishant, additional, Schafernak, Kristian T., additional, Henry, Michael M., additional, van Halteren, Astrid G. S., additional, Abla, Oussama, additional, Diamond, Eli L., additional, and Emile, Jean-François, additional

Published
2022
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36. HPV vaccination to prevent recurrence of anal intraepithelial neoplasia in HIV+ MSM: a randomised, placebo-controlled multicentre trial

Author

Gosens, Karien C M, van der Zee, Ramon P, van Heukelom, Matthijs L Siegenbeek, Jongen, Vita W, Cairo, Irina, van Eeden, Arne, van Noesel, Carel J M, Quint, Wim G V, Pasmans, Hella, Dijkgraaf, Marcel G W, de Vries, Henry J C, Prins, Jan M, Pathology, Dermatology, AII - Infectious diseases, Graduate School, Cancer Center Amsterdam, Amsterdam institute for Infection and Immunity, CCA - Cancer Treatment and Quality of Life, APH - Methodology, APH - Global Health, Epidemiology and Data Science, and Infectious diseases

Abstract

OBJECTIVE: Anal cancer precursor lesions high-grade anal intraepithelial neoplasia (HGAIN) are highly prevalent among HIV+ MSM. Treatment of HGAIN is frustrated by high recurrence rates. We investigated the efficacy of the quadrivalent human papillomavirus (qHPV) vaccine as posttreatment adjuvant in preventing HGAIN recurrence in HIV+ MSM. DESIGN: Randomized, double-blind, placebo-controlled, multicentre trial. SETTING: Three HIV outpatient clinics in Amsterdam, the Netherlands. SUBJECTS: HIV+ MSM with CD4+ cell count more than 350 cells/μl, biopsy-proven intra-anal HGAIN successfully treated in the past year, and lesions still in remission at enrolment, as assessed by high-resolution anoscopy (HRA). INTERVENTION: Participants were randomized to three doses of qHPV (Gardasil-4, MSD) or placebo with vaccinations at 0, 2, and 6 months. HRA was repeated at 6, 12, and 18 months. MAIN OUTCOME MEASURE: The primary outcome was cumulative, biopsy-proven HGAIN recurrence rate at 18 months, evaluated in an intention-to-treat (ITT) (received all vaccinations) and per-protocol analysis (all vaccinations and complete follow-up). RESULTS: We randomized 126 participants of which 64 (50.8%) received qHPV and 62 (49.2%) placebo. All participants received three vaccinations, and in both groups for two participants follow-up was incomplete. We found no difference (P = 0.38) in cumulative HGAIN recurrence rates between the qHPV (44/64, 68.8%) and placebo group (38/62, 61.3%) in the ITT analysis [absolute risk reduction -7.5 (95% confidence interval (CI) -24.1 to 9.2)]. This was similar in the per-protocol analysis. CONCLUSION: Despite adequate serological responses to qHPV vaccination, short-term recurrence of HGAIN was not prevented. These findings do not support qHPV vaccination as a treatment adjuvant to prevent HGAIN recurrence in HIV+ MSM.

Published
2021
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38. Increased prevalence of BRCA1/2 mutations in women with macrotextured breast implants and anaplastic large cell lymphoma of the breast

Author

de Boer, Mintsje, primary, Hauptmann, Michael, additional, Hijmering, Nathalie J., additional, van Noesel, Carel J. M., additional, Rakhorst, Hinne A., additional, Meijers-Heijboer, Hanne E. J., additional, de Boer, Jan Paul, additional, van der Hulst, René R. W. J., additional, de Jong, Daphne, additional, and van Leeuwen, Flora E., additional

Published
2020
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40. Cancer Risk Stratification of Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus–Positive Men by Validated Methylation Markers Associated With Progression to Cancer

Author

van der Zee, Ramon P, primary, Richel, Olivier, additional, van Noesel, Carel J M, additional, Ciocănea-Teodorescu, Iuliana, additional, van Splunter, Annina P, additional, ter Braak, Timo J, additional, Nathan, Mayura, additional, Cuming, Tamzin, additional, Sheaff, Michael, additional, Kreuter, Alexander, additional, Meijer, Chris J L M, additional, Quint, Wim G V, additional, de Vries, Henry J C, additional, Prins, Jan M, additional, and Steenbergen, Renske D M, additional

Published
2020
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41. The bone morphogenetic protein pathway is active in human colon adenomas and inactivated in colorectal cancer

Author

Kodach, Liudmila L., Bleuming, Sylvia A., Musler, Alex R., Peppelenbosch, Maikel P., Hommes, Daniel W., van den Brink, Gijs R., van Noesel, Carel J. M., Offerhaus, G. Johan A., and Hardwick, James C.H.

Subjects
Bone morphogenetic proteins -- Physiological aspects, Bone morphogenetic proteins -- Research, Colorectal cancer -- Development and progression, Adenoma -- Development and progression, Tissue microarrays -- Analysis, Health
Published
2008

42. Higher‐order of chronic lymphocytic leukaemia (CLL) classification: shared antigenic specificities of stereotyped B‐cell receptor subsets as defined by the European Research Initiative on CLL consortium.

Author

Bende, Richard J., Janssen, Jerry, and van Noesel, Carel J. M.

Subjects
LYMPHOCYTIC leukemia, CHRONIC leukemia, CHRONIC lymphocytic leukemia, IMMUNOGLOBULIN light chains, SJOGREN'S syndrome, RHEUMATOID factor
Abstract

Recently, an update on the analyses of the immunoglobulin heavy variable region chain (IGHV-IGHD-IGHJ) gene rearrangements of a comprehensive cohort, now containing 29 856 cases of chronic lymphocytic leukaemia (CLL), was reported by the European Research Initiative on CLL (ERIC) consortium.1 Within this collection, as many as 2195 stereotyped B-cell receptor (BCR) subsets have been defined ranging in size from 2 to 764 IGHV sequences. ht 1 Stereotyped rheumatoid factors (RFs) expressed by MALT lymphomas (MALT-L) have been described previously.8 The numbers of stereotyped RFs expressed by salivary gland MALT-L have been updated. Higher-order of chronic lymphocytic leukaemia (CLL) classification: shared antigenic specificities of stereotyped B-cell receptor subsets as defined by the European Research Initiative on CLL consortium Identification of a novel stereotypic IGHV4-59/IGHJ5-encoded B-cell receptor subset expressed by various B-cell lymphomas with high affinity rheumatoid factor activity. [Extracted from the article]

Published
2022
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44. Apparent Lack of BRAFV600E Derived HLA Class I Presented Neoantigens Hampers Neoplastic Cell Targeting by CD8+ T Cells in Langerhans Cell Histiocytosis

Author

Kemps, Paul G., primary, Zondag, Timo C., additional, Steenwijk, Eline C., additional, Andriessen, Quirine, additional, Borst, Jelske, additional, Vloemans, Sandra, additional, Roelen, Dave L., additional, Voortman, Lenard M., additional, Verdijk, Robert M., additional, van Noesel, Carel J. M., additional, Cleven, Arjen H. G., additional, Hawkins, Cynthia, additional, Lang, Veronica, additional, de Ru, Arnoud H., additional, Janssen, George M. C., additional, Haasnoot, Geert W., additional, Franken, Kees L. M. C., additional, van Eijk, Ronald, additional, Solleveld-Westerink, Nienke, additional, van Wezel, Tom, additional, Egeler, R. Maarten, additional, Beishuizen, Auke, additional, van Laar, Jan A. M., additional, Abla, Oussama, additional, van den Bos, Cor, additional, van Veelen, Peter A., additional, and van Halteren, Astrid G. S., additional

Published
2020
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45. Absence of PD-L1 expression on tumor cells in the context of an activated immune infiltrate may indicate impaired IFNγ signaling in non-small cell lung cancer

Author

Theelen, Willemijn S. M. E., primary, Kuilman, Thomas, additional, Schulze, Katja, additional, Zou, Wei, additional, Krijgsman, Oscar, additional, Peters, Dennis D. G. C., additional, Cornelissen, Sten, additional, Monkhorst, Kim, additional, Sarma, Pranamee, additional, Sumiyoshi, Teiko, additional, Amler, Lukas C., additional, Willems, Stefan M., additional, Blaauwgeers, Johannes L. G., additional, van Noesel, Carel J. M., additional, Peeper, Daniel S., additional, van den Heuvel, Michel M., additional, and Kowanetz, Marcin, additional

Published
2019
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46. Absence of PD-L1 expression on tumor cells in the context of an activated immune infiltrate may indicate impaired IFNγ signaling in non-small cell lung cancer

Author

Theelen, Willemijn S M E, Kuilman, Thomas, Schulze, Katja, Zou, Wei, Krijgsman, Oscar, Peters, Dennis D G C, Cornelissen, Sten, Monkhorst, Kim, Sarma, Pranamee, Sumiyoshi, Teiko, Amler, Lukas C, Willems, Stefan M, Blaauwgeers, Johannes L G, van Noesel, Carel J M, Peeper, Daniel S, van den Heuvel, Michel M, Kowanetz, Marcin, Theelen, Willemijn S M E, Kuilman, Thomas, Schulze, Katja, Zou, Wei, Krijgsman, Oscar, Peters, Dennis D G C, Cornelissen, Sten, Monkhorst, Kim, Sarma, Pranamee, Sumiyoshi, Teiko, Amler, Lukas C, Willems, Stefan M, Blaauwgeers, Johannes L G, van Noesel, Carel J M, Peeper, Daniel S, van den Heuvel, Michel M, and Kowanetz, Marcin

Published
2019

47. Recommendations for the clinical interpretation and reporting of copy number gains using gene panel NGS analysis in routine diagnostics

Author

Pathologie Laboratorium diagnostiek, Pathologie Pathologen staf, Cancer, Eijkelenboom, Astrid, Tops, Bastiaan B J, van den Berg, Anke, van den Brule, Adrianus J C, Dinjens, Winand N M, Dubbink, Hendrikus J, Ter Elst, Arja, Geurts-Giele, Willemina R R, Groenen, Patricia J T A, Groenendijk, Floris H, Heideman, Daniëlle A M, Huibers, Manon M H, Huijsmans, Cornelis J J, Jeuken, Judith W M, van Kempen, Léon C, Korpershoek, Esther, Kroeze, Leonie I, de Leng, Wendy W J, van Noesel, Carel J M, Speel, Ernst-Jan M, Vogel, Maartje J, van Wezel, Tom, Nederlof, Petra M, Schuuring, Ed, Ligtenberg, Marjolijn J L, Pathologie Laboratorium diagnostiek, Pathologie Pathologen staf, Cancer, Eijkelenboom, Astrid, Tops, Bastiaan B J, van den Berg, Anke, van den Brule, Adrianus J C, Dinjens, Winand N M, Dubbink, Hendrikus J, Ter Elst, Arja, Geurts-Giele, Willemina R R, Groenen, Patricia J T A, Groenendijk, Floris H, Heideman, Daniëlle A M, Huibers, Manon M H, Huijsmans, Cornelis J J, Jeuken, Judith W M, van Kempen, Léon C, Korpershoek, Esther, Kroeze, Leonie I, de Leng, Wendy W J, van Noesel, Carel J M, Speel, Ernst-Jan M, Vogel, Maartje J, van Wezel, Tom, Nederlof, Petra M, Schuuring, Ed, and Ligtenberg, Marjolijn J L

Published
2019

48. Host Cell Deoxyribonucleic Acid Methylation Markers for the Detection of High-grade Anal Intraepithelial Neoplasia and Anal Cancer

Author

van der Zee, Ramon P, primary, Richel, Olivier, additional, van Noesel, Carel J M, additional, Novianti, Putri W, additional, Ciocanea-Teodorescu, Iuliana, additional, van Splunter, Annina P, additional, Duin, Sylvia, additional, van den Berk, Guido E L, additional, Meijer, Chris J L M, additional, Quint, Wim G V, additional, de Vries, Henry J C, additional, Prins, Jan M, additional, and Steenbergen, Renske D M, additional

Published
2018
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49. Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial

Author

Teulings, Hansje-Eva, primary, Tjin, Esther P. M., additional, Willemsen, Karina J., additional, van der Kleij, Stephanie, additional, Meulen, Sylvia ter, additional, Kemp, E. Helen, additional, Krebbers, Gabrielle, additional, van Noesel, Carel J. M., additional, Franken, Cornelis L. M. C., additional, Drijfhout, Jan W., additional, Melief, Cornelis J. M., additional, Nieuweboer-Krobotova, Ludmila, additional, Nieweg, Omgo E., additional, Hage, Jos A. van der, additional, van der Veen, J. P. Wietze, additional, Relyveld, Germaine N., additional, and Luiten, Rosalie M., additional

Published
2018
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50. Apparent Lack of BRAF V600E Derived HLA Class I Presented Neoantigens Hampers Neoplastic Cell Targeting by CD8+ T Cells in Langerhans Cell Histiocytosis.

Author

Kemps, Paul G., Zondag, Timo C., Steenwijk, Eline C., Andriessen, Quirine, Borst, Jelske, Vloemans, Sandra, Roelen, Dave L., Voortman, Lenard M., Verdijk, Robert M., van Noesel, Carel J. M., Cleven, Arjen H. G., Hawkins, Cynthia, Lang, Veronica, de Ru, Arnoud H., Janssen, George M. C., Haasnoot, Geert W., Franken, Kees L. M. C., van Eijk, Ronald, Solleveld-Westerink, Nienke, and van Wezel, Tom

Subjects
LANGERHANS-cell histiocytosis, T cells, HLA histocompatibility antigens, BINDING site assay, HISTOCOMPATIBILITY class I antigens, CELL lines, ERDHEIM-Chester disease
Abstract

Langerhans Cell Histiocytosis (LCH) is a neoplastic disorder of hematopoietic origin characterized by inflammatory lesions containing clonal histiocytes (LCH-cells) intermixed with various immune cells, including T cells. In 50–60% of LCH-patients, the somatic BRAF V600E driver mutation, which is common in many cancers, is detected in these LCH-cells in an otherwise quiet genomic landscape. Non-synonymous mutations like BRAF V600E can be a source of neoantigens capable of eliciting effective antitumor CD8+ T cell responses. This requires neopeptides to be stably presented by Human Leukocyte Antigen (HLA) class I molecules and sufficient numbers of CD8+ T cells at tumor sites. Here, we demonstrate substantial heterogeneity in CD8+ T cell density in n = 101 LCH-lesions, with BRAF V600E mutated lesions displaying significantly lower CD8+ T cell:CD1a+ LCH-cell ratios (p = 0.01) than BRAF wildtype lesions. Because LCH-lesional CD8+ T cell density had no significant impact on event-free survival, we investigated whether the intracellularly expressed BRAF V600E protein is degraded into neopeptides that are naturally processed and presented by cell surface HLA class I molecules. Epitope prediction tools revealed a single HLA class I binding BRAF V600E derived neopeptide (KIGDFGLAT E K), which indeed displayed strong to intermediate binding capacity to HLA-A*03:01 and HLA-A*11:01 in an in vitro peptide-HLA binding assay. Mass spectrometry-based targeted peptidomics was used to investigate the presence of this neopeptide in HLA class I presented peptides isolated from several BRAF V600E expressing cell lines with various HLA genotypes. While the HLA-A*02:01 binding BRAF wildtype peptide KIGDFGLAT V was traced in peptides isolated from all five cell lines expressing this HLA subtype, KIGDFGLAT E K was not detected in the HLA class I peptidomes of two distinct BRAF V600E transduced cell lines with confirmed expression of HLA-A*03:01 or HLA-A*11:01. These data indicate that the in silico predicted HLA class I binding and proteasome-generated neopeptides derived from the BRAF V600E protein are not presented by HLA class I molecules. Given that the BRAF V600E mutation is highly prevalent in chemotherapy refractory LCH-patients who may qualify for immunotherapy, this study therefore questions the efficacy of immune checkpoint inhibitor therapy in LCH. [ABSTRACT FROM AUTHOR]

Published
2020
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