Integrative molecular characterization of malignant pleural mesothelioma

TCGA Research Network

doi:10.1158/2159-8290.CD-18-0804

Integrative molecular characterization of malignant pleural mesothelioma

TCGA Research Network

Research output: Contribution to journal › Article › peer-review

429 Citations (Scopus)

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 expresssion of the immune-checkpoint gene VISTA in epithelioid MPM.

Original language	English
Pages (from-to)	1549-1565
Number of pages	17
Journal	Cancer Discovery
Volume	8
Issue number	12
DOIs	https://doi.org/10.1158/2159-8290.CD-18-0804
Publication status	Published - 1 Dec 2018

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10.1158/2159-8290.CD-18-0804

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@article{ef969b2c812841849322ccae4d19496f,

title = "Integrative molecular characterization of malignant pleural mesothelioma",

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 expresssion of the immune-checkpoint gene VISTA in epithelioid MPM.",

author = "{TCGA Research Network} and Julija Hmeljak and Francisco Sanchez-Vega and Hoadley, {Katherine A.} and Juliann Shih and Chip Stewart and David Heiman and Patrick Tarpey and Ludmila Danilova and Esther Drill and Gibb, {Ewan A.} and Reanne Bowlby and Rupa Kanchi and Hatice Osmanbeyoglu and Yoshitaka Sekido and Jumpei Takeshita and Yulia Newton and Kiley Graim and Manaswi Gupta and Gay, {Carl M.} and Lixia Diao and Gibbs, {David L.} and Vesteinn Thorsson and Lisa Iype and Havish Kantheti and Severson, {David T.} and Gloria Ravegnini and Patrice Desmeules and Jungbluth, {Achim A.} and Travis, {William D.} and Sanja Dacic and Chirieac, {Lucian R.} and Fran{\c c}oise Galateau-Sall{\'e} and Junya Fujimoto and Husain, {Aliya N.} and Silveira, {Henrique C.S.} and Valerie Rusch and Rintoul, {Robert C.} and Harvey Pass and Hedy Kindler and Zauderer, {Marjorie G.} and Kwiatkowski, {David J.} and Raphael Bueno and Anne Tsao and Jenette Creaney and Tara Lichtenberg and Kristen Leraas and Jay Bowen and Ina Felau and Zenklusen, {Jean Claude} and Rehan Akbani and Cherniack, {Andrew D.} and Byers, {Lauren Averett} and Noble, {Michael S.} and Fletcher, {Jonathan A.} and Robertson, {A. Gordon} and Ronglai Shen and Hiroyuki Aburatani and Robinson, {Bruce W.} and Peter Campbell and Marc Ladanyi and Adrian Ally and Pavana Anur and Joshua Armenia and Auman, {J. Todd} and Miruna Balasundaram and Saianand Balu and Baylin, {Stephen B.} and Michael Becich and Carmen Behrens and Rameen Beroukhim and Craig Bielski and Tom Bodenheimer and Bootwalla, {Moiz S.} and Denise Brooks and Byers, {Lauren Averett} and C{\'a}rcano, {Fl{\'a}vio M.} and Rebecca Carlsen and Carvalho, {Andre L.} and Dorothy Cheung and Lucian Chirieac and Juok Cho and Eric Chuah and Sudha Chudamani and Carrie Cibulskis and Leslie Cope and Daniel Crain and Erin Curley and {De Rienzo}, Assunta and Timothy DeFreitas and Demchok, {John A.} and Noreen Dhalla and Rajiv Dhir and Michael Feldman and Ferguson, {Martin L.} and Shiro Fukuda and Gabriel, {Stacey B.} and Sall{\'e}, {Fran{\c c}oise Galateau} and Jianjiong Gao and Johanna Gardner and Gastier-Foster, {Julie M.} and Nils Gehlenborg and Mark Gerken and Gad Getz and Chandra Goparaju and Benjamin Gross and Guangwu Guo and Seiki Hasegawa and David Haussler and Hayes, {D. Neil} and Heiman, {David I.} and Zachary Heins and Holt, {Robert A.} and Hoyle, {Alan P.} and Aliya Husain and Hutter, {Carolyn M.} and Jefferys, {Stuart R.} and Jones, {Steven J.M.} and Jones, {Corbin D.} and Kanchi, {Rupa S.} and Katayoon Kasaian and Jaegil Kim and Nobuyuki Kondo and Thomas Krausz and Ritika Kundra and Kozo Kuribayashi and Lai, {Phillip H.} and Laird, {Peter W.} and Lawrence, {Michael S.} and Darlene Lee and Leraas, {Kristen M.} and Lichtenberg, {Tara M.} and Pei Lin and Jia Liu and Wenbin Liu and Liu, {Eric Minwei} and Laxmi Lolla and Adhemar Longatto-Filho and Yiling Lu and James Luketich and Yussanne Ma and Maglinte, {Dennis T.} and David Mallory and Marra, {Marco A.} and Michael Mayo and Sam Meier and Jonathan Melamed and Shaowu Meng and Matthew Meyerson and Mieczkowski, {Piotr A.} and Mills, {Gordon B.} and Moore, {Richard A.} and Cesar Moran and Scott Morris and Mose, {Lisle E.} and Mungall, {Andrew J.} and Karen Mungall and Takashi Nakano and Rashi Naresh and Angelica Ochoa and Hatice Osmanbeyoglu and Parker, {Joel S.} and Pass, {Harvey I.} and Joseph Paulauskis and Arjun Pennathur and Pennell, {Nathan A.} and Robert Penny and Perou, {Charles M.} and Todd Pihl and Ramirez, {Nilsa C.} and Rassl, {Doris M.} and Glen Reid and Reis, {Rui M.} and Reynolds, {Sheila M.} and David Rice and Richards, {William G.} and Jeffrey Roach and Valerie Rusch and Sara Sadeghi and Gordon Saksena and Chris Sander and Ayuko Sato and Cristovam Scapulatempo-Neto and Schein, {Jacqueline E.} and Nikolaus Schultz and Schumacher, {Steven E.} and Tanguy Seiwert and Candace Shelton and Troy Shelton and Robert Sheridan and Yan Shi and Yuichi Shiraishi and Ilya Shmulevich and Silveira, {Henrique C.S.} and Simons, {Janae V.} and Payal Sipahimalani and Tara Skelly and Sofia, {Heidi J.} and Soloway, {Matthew G.} and Paul Spellman and Josh Stuart and Qiang Sun and Angela Tam and Donghui Tan and Roy Tarnuzzer and Kenji Tatsuno and Taylor, {Barry S.} and Nina Thiessen and Eric Thompson and Anne Tsao and Kane Tse and Tohru Tsujimura and Federico Valdivieso and {Van Den Berg}, {David J.} and {van Zandwijk}, Nico and Umadevi Veluvolu and Viana, {Luciano S.} and Douglas Voet and Yunhu Wan and Zhining Wang and Jing Wang and Joellen Weaver and Weinstein, {John N.} and Weisenberger, {Daniel J.} and Wilkerson, {Matthew D.} and Lisa Wise and Ignacio Wistuba and Tina Wong and Ye Wu and Shogo Yamamoto and Liming Yang and Zenklusen, {Jean C.} and Jiashan Zhang and Hailei Zhang and Hongxin Zhang and Erik Zmuda",

year = "2018",

month = dec,

day = "1",

doi = "10.1158/2159-8290.CD-18-0804",

language = "English",

volume = "8",

pages = "1549--1565",

journal = "Cancer Discovery",

issn = "2159-8274",

publisher = "American Association for Cancer Research Inc.",

number = "12",

}

TY - JOUR

T1 - Integrative molecular characterization of malignant pleural mesothelioma

AU - TCGA Research Network

AU - Hmeljak, Julija

AU - Sanchez-Vega, Francisco

AU - Hoadley, Katherine A.

AU - Shih, Juliann

AU - Stewart, Chip

AU - Heiman, David

AU - Tarpey, Patrick

AU - Danilova, Ludmila

AU - Drill, Esther

AU - Gibb, Ewan A.

AU - Bowlby, Reanne

AU - Kanchi, Rupa

AU - Osmanbeyoglu, Hatice

AU - Sekido, Yoshitaka

AU - Takeshita, Jumpei

AU - Newton, Yulia

AU - Graim, Kiley

AU - Gupta, Manaswi

AU - Gay, Carl M.

AU - Diao, Lixia

AU - Gibbs, David L.

AU - Thorsson, Vesteinn

AU - Iype, Lisa

AU - Kantheti, Havish

AU - Severson, David T.

AU - Ravegnini, Gloria

AU - Desmeules, Patrice

AU - Jungbluth, Achim A.

AU - Travis, William D.

AU - Dacic, Sanja

AU - Chirieac, Lucian R.

AU - Galateau-Sallé, Françoise

AU - Fujimoto, Junya

AU - Husain, Aliya N.

AU - Silveira, Henrique C.S.

AU - Rusch, Valerie

AU - Rintoul, Robert C.

AU - Pass, Harvey

AU - Kindler, Hedy

AU - Zauderer, Marjorie G.

AU - Kwiatkowski, David J.

AU - Bueno, Raphael

AU - Tsao, Anne

AU - Creaney, Jenette

AU - Lichtenberg, Tara

AU - Leraas, Kristen

AU - Bowen, Jay

AU - Felau, Ina

AU - Zenklusen, Jean Claude

AU - Akbani, Rehan

AU - Cherniack, Andrew D.

AU - Byers, Lauren Averett

AU - Noble, Michael S.

AU - Fletcher, Jonathan A.

AU - Robertson, A. Gordon

AU - Shen, Ronglai

AU - Aburatani, Hiroyuki

AU - Robinson, Bruce W.

AU - Campbell, Peter

AU - Ladanyi, Marc

AU - Ally, Adrian

AU - Anur, Pavana

AU - Armenia, Joshua

AU - Auman, J. Todd

AU - Balasundaram, Miruna

AU - Balu, Saianand

AU - Baylin, Stephen B.

AU - Becich, Michael

AU - Behrens, Carmen

AU - Beroukhim, Rameen

AU - Bielski, Craig

AU - Bodenheimer, Tom

AU - Bootwalla, Moiz S.

AU - Brooks, Denise

AU - Byers, Lauren Averett

AU - Cárcano, Flávio M.

AU - Carlsen, Rebecca

AU - Carvalho, Andre L.

AU - Cheung, Dorothy

AU - Chirieac, Lucian

AU - Cho, Juok

AU - Chuah, Eric

AU - Chudamani, Sudha

AU - Cibulskis, Carrie

AU - Cope, Leslie

AU - Crain, Daniel

AU - Curley, Erin

AU - De Rienzo, Assunta

AU - DeFreitas, Timothy

AU - Demchok, John A.

AU - Dhalla, Noreen

AU - Dhir, Rajiv

AU - Feldman, Michael

AU - Ferguson, Martin L.

AU - Fukuda, Shiro

AU - Gabriel, Stacey B.

AU - Sallé, Françoise Galateau

AU - Gao, Jianjiong

AU - Gardner, Johanna

AU - Gastier-Foster, Julie M.

AU - Gehlenborg, Nils

AU - Gerken, Mark

AU - Getz, Gad

AU - Goparaju, Chandra

AU - Gross, Benjamin

AU - Guo, Guangwu

AU - Hasegawa, Seiki

AU - Haussler, David

AU - Hayes, D. Neil

AU - Heiman, David I.

AU - Heins, Zachary

AU - Holt, Robert A.

AU - Hoyle, Alan P.

AU - Husain, Aliya

AU - Hutter, Carolyn M.

AU - Jefferys, Stuart R.

AU - Jones, Steven J.M.

AU - Jones, Corbin D.

AU - Kanchi, Rupa S.

AU - Kasaian, Katayoon

AU - Kim, Jaegil

AU - Kondo, Nobuyuki

AU - Krausz, Thomas

AU - Kundra, Ritika

AU - Kuribayashi, Kozo

AU - Lai, Phillip H.

AU - Laird, Peter W.

AU - Lawrence, Michael S.

AU - Lee, Darlene

AU - Leraas, Kristen M.

AU - Lichtenberg, Tara M.

AU - Lin, Pei

AU - Liu, Jia

AU - Liu, Wenbin

AU - Liu, Eric Minwei

AU - Lolla, Laxmi

AU - Longatto-Filho, Adhemar

AU - Lu, Yiling

AU - Luketich, James

AU - Ma, Yussanne

AU - Maglinte, Dennis T.

AU - Mallory, David

AU - Marra, Marco A.

AU - Mayo, Michael

AU - Meier, Sam

AU - Melamed, Jonathan

AU - Meng, Shaowu

AU - Meyerson, Matthew

AU - Mieczkowski, Piotr A.

AU - Mills, Gordon B.

AU - Moore, Richard A.

AU - Moran, Cesar

AU - Morris, Scott

AU - Mose, Lisle E.

AU - Mungall, Andrew J.

AU - Mungall, Karen

AU - Nakano, Takashi

AU - Naresh, Rashi

AU - Ochoa, Angelica

AU - Osmanbeyoglu, Hatice

AU - Parker, Joel S.

AU - Pass, Harvey I.

AU - Paulauskis, Joseph

AU - Pennathur, Arjun

AU - Pennell, Nathan A.

AU - Penny, Robert

AU - Perou, Charles M.

AU - Pihl, Todd

AU - Ramirez, Nilsa C.

AU - Rassl, Doris M.

AU - Reid, Glen

AU - Reis, Rui M.

AU - Reynolds, Sheila M.

AU - Rice, David

AU - Richards, William G.

AU - Roach, Jeffrey

AU - Rusch, Valerie

AU - Sadeghi, Sara

AU - Saksena, Gordon

AU - Sander, Chris

AU - Sato, Ayuko

AU - Scapulatempo-Neto, Cristovam

AU - Schein, Jacqueline E.

AU - Schultz, Nikolaus

AU - Schumacher, Steven E.

AU - Seiwert, Tanguy

AU - Shelton, Candace

AU - Shelton, Troy

AU - Sheridan, Robert

AU - Shi, Yan

AU - Shiraishi, Yuichi

AU - Shmulevich, Ilya

AU - Silveira, Henrique C.S.

AU - Simons, Janae V.

AU - Sipahimalani, Payal

AU - Skelly, Tara

AU - Sofia, Heidi J.

AU - Soloway, Matthew G.

AU - Spellman, Paul

AU - Stuart, Josh

AU - Sun, Qiang

AU - Tam, Angela

AU - Tan, Donghui

AU - Tarnuzzer, Roy

AU - Tatsuno, Kenji

AU - Taylor, Barry S.

AU - Thiessen, Nina

AU - Thompson, Eric

AU - Tsao, Anne

AU - Tse, Kane

AU - Tsujimura, Tohru

AU - Valdivieso, Federico

AU - Van Den Berg, David J.

AU - van Zandwijk, Nico

AU - Veluvolu, Umadevi

AU - Viana, Luciano S.

AU - Voet, Douglas

AU - Wan, Yunhu

AU - Wang, Zhining

AU - Wang, Jing

AU - Weaver, Joellen

AU - Weinstein, John N.

AU - Weisenberger, Daniel J.

AU - Wilkerson, Matthew D.

AU - Wise, Lisa

AU - Wistuba, Ignacio

AU - Wong, Tina

AU - Wu, Ye

AU - Yamamoto, Shogo

AU - Yang, Liming

AU - Zenklusen, Jean C.

AU - Zhang, Jiashan

AU - Zhang, Hailei

AU - Zhang, Hongxin

AU - Zmuda, Erik

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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 expresssion of the immune-checkpoint gene VISTA in epithelioid MPM.

AB - 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 expresssion of the immune-checkpoint gene VISTA in epithelioid MPM.

UR - http://www.scopus.com/inward/record.url?scp=85058055377&partnerID=8YFLogxK

U2 - 10.1158/2159-8290.CD-18-0804

DO - 10.1158/2159-8290.CD-18-0804

M3 - Article

C2 - 30322867

AN - SCOPUS:85058055377

SN - 2159-8274

VL - 8

SP - 1549

EP - 1565

JO - Cancer Discovery

JF - Cancer Discovery

IS - 12

ER -

Integrative molecular characterization of malignant pleural mesothelioma

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