Integrative Molecular Characterization of Malignant Pleural Mesothelioma
Authors: Julija Hmeljak, Francisco Sanchez-Vega, Katherine A. Hoadley, Juliann Shih, Chip Stewart, David Heiman, Patrick Tarpey, Ludmila Danilova, Esther Drill, Ewan A. Gibb, Reanne Bowlby, Rupa Kanchi, Hatice U. Osmanbeyoglu, Yoshitaka Sekido, Jumpei Takeshita, Yulia Newton, Kiley Graim, Manaswi Gupta, Carl M. Gay, Lixia Diao, David L. Gibbs, Vesteinn Thorsson, Lisa Iype, Havish Kantheti, David T. Severson, Gloria Ravegnini, Patrice Desmeules, Achim A. Jungbluth, William D. Travis, Sanja Dacic, Lucian R. Chirieac, Françoise Galateau-Sallé, Junya Fujimoto, Aliya N. Husain, Henrique C. Silveira, Valerie W. Rusch, Robert C. Rintoul, Harvey Pass, Hedy Kindler, Marjorie G. Zauderer, David J. Kwiatkowski, Raphael Bueno, Anne S. Tsao, Jenette Creaney, Tara Lichtenberg, Kristen Leraas, Jay Bowen, Ina Felau, Jean Claude Zenklusen, Rehan Akbani, Andrew D. Cherniack, Lauren A. Byers, Michael S. Noble, Jonathan A. Fletcher, A. Gordon Robertson, Ronglai Shen, Hiroyuki Aburatani, Bruce W. Robinson, Peter Campbell, Marc Ladanyi, Hiroyuki Aburatani, Rehan Akbani, Adrian Ally, Pavana Anur, Joshua Armenia, J. Todd Auman, Miruna Balasundaram, Saianand Balu, Stephen B. Baylin, Michael Becich, Carmen Behrens, Rameen Beroukhim, Craig Bielski, Tom Bodenheimer, Moiz S. Bootwalla, Jay Bowen, Reanne Bowlby, Denise Brooks, Raphael Bueno, Lauren Averett Byers, Flávio M. Cárcano, Rebecca Carlsen, Andre L. Carvalho, Andrew D. Cherniack, Dorothy Cheung, Lucian Chirieac, Juok Cho, Eric Chuah, Sudha Chudamani, Carrie Cibulskis, Leslie Cope, Daniel Crain, Jenette Creaney, Erin Curley, Sanja Dacic, Ludmila Danilova, Assunta De Rienzo, Timothy DeFreitas, John A. Demchok, Noreen Dhalla, Rajiv Dhir, Lixia Diao, Esther Drill, Ina Felau, Michael Feldman, Martin L. Ferguson, Jonathan A. Fletcher, Junya Fujimoto, Junya Fujimoto, Shiro Fukuda, Stacey B. Gabriel, Françoise Galateau Sallé, Jianjiong Gao, Johanna Gardner, Julie M. Gastier-Foster, Carl M. Gay, Nils Gehlenborg, Mark Gerken, Gad Getz, Ewan A. Gibb, David L. Gibbs, Chandra Goparaju, Kiley Graim, Benjamin Gross, Guangwu Guo, Manaswi Gupta, Seiki Hasegawa, David Haussler, D. Neil Hayes, David I. Heiman, Zachary Heins, Julija Hmeljak, Katherine A. Hoadley, Robert A. Holt, Alan P. Hoyle, Aliya Husain, Carolyn M. Hutter, Lisa Iype, Stuart R. Jefferys, Steven J.M. Jones, Corbin D. Jones, Rupa S. Kanchi, Katayoon Kasaian, Jaegil Kim, Hedy Kindler, Nobuyuki Kondo, Thomas Krausz, Ritika Kundra, Kozo Kuribayashi, David J. Kwiatkowski, Marc Ladanyi, Phillip H. Lai, Peter W. Laird, Michael S. Lawrence, Darlene Lee, Kristen M. Leraas, Tara M. Lichtenberg, Pei Lin, Jia Liu, Wenbin Liu, Eric Minwei Liu, Laxmi Lolla, Adhemar Longatto-Filho, Yiling Lu, James Luketich, Yussanne Ma, Dennis T. Maglinte, David Mallory, Marco A. Marra, Michael Mayo, Sam Meier, Jonathan Melamed, Shaowu Meng, Matthew Meyerson, Piotr A. Mieczkowski, Gordon B. Mills, Richard A. Moore, Cesar Moran, Scott Morris, Lisle E. Mose, Andrew J. Mungall, Karen Mungall, Takashi Nakano, Rashi Naresh, Yulia Newton, Michael S. Noble, Angelica Ochoa, Hatice Osmanbeyoglu, Joel S. Parker, Harvey I. Pass, Joseph Paulauskis, Arjun Pennathur, Nathan A. Pennell, Robert Penny, Charles M. Perou, Todd Pihl, Nilsa C. Ramirez, Doris M. Rassl, Gloria Ravegnini, Glen Reid, Rui M. Reis, Sheila M. Reynolds, David Rice, William G Richards, Robert C. Rintoul, Jeffrey Roach, A. Gordon Robertson, Valerie Rusch, Sara Sadeghi, Gordon Saksena, Francisco Sanchez-Vega, Chris Sander, Ayuko Sato, Cristovam Scapulatempo-Neto, Jacqueline E. Schein, Nikolaus Schultz, Steven E. Schumacher, Tanguy Seiwert, Yoshitaka Sekido, David T Severson, Candace Shelton, Troy Shelton, Ronglai Shen, Robert Sheridan, Yan Shi, Juliann Shih, Yuichi Shiraishi, Ilya Shmulevich, Henrique C. S. Silveira, Janae V. Simons, Payal Sipahimalani, Tara Skelly, Heidi J. Sofia, Matthew G. Soloway, Paul Spellman, Chip Stewart, Josh Stuart, Qiang Sun, Jumpei Takeshita, Angela Tam, Donghui Tan, Roy Tarnuzzer, Kenji Tatsuno, Barry S Taylor, Nina Thiessen, Eric Thompson, Vesteinn Thorsson, William D. Travis, Anne Tsao, Kane Tse, Tohru Tsujimura, Federico Valdivieso, David J. Van Den Berg, Nico van Zandwijk, Umadevi Veluvolu, Luciano S. Viana, Douglas Voet, Yunhu Wan, Zhining Wang, Jing Wang, Joellen Weaver, John N. Weinstein, Daniel J. Weisenberger, Matthew D. Wilkerson, Lisa Wise, Ignacio Wistuba, Tina Wong, Ye Wu, Shogo Yamamoto, Liming Yang, Marjorie G. Zauderer, Jean C. Zenklusen, Jiashan Zhang, Hailei Zhang, Hongxin Zhang, Erik Zmuda
Journal: Cancer Discovery (2018)

Abstract Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options. Significance: Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene VISTA in epithelioid MPM. See related commentary by Aggarwal and Albelda, p. 1508. This article is highlighted in the In This Issue feature, p. 1494