Format

Send to

Choose Destination
Cancer Discov. 2018 Dec;8(12):1548-1565. doi: 10.1158/2159-8290.CD-18-0804. Epub 2018 Oct 15.

Integrative Molecular Characterization of Malignant Pleural Mesothelioma.

Collaborators (216)

Aburatani H, Akbani R, Ally A, Anur P, Armenia J, Auman JT, Balasundaram M, Balu S, Baylin SB, Becich M, Behrens C, Beroukhim R, Bielski C, Bodenheimer T, Bootwalla MS, Bowen J, Bowlby R, Brooks D, Bueno R, Byers LA, Cárcano FM, Carlsen R, Carvalho AL, Cherniack AD, Cheung D, Chirieac L, Cho J, Chuah E, Chudamani S, Cibulskis C, Cope L, Crain D, Creaney J, Curley E, Dacic S, Danilova L, Rienzo A, DeFreitas T, Demchok JA, Dhalla N, Dhir R, Diao L, Drill E, Felau I, Feldman M, Ferguson ML, Fletcher JA, Fujimoto J, Fujimoto J, Fukuda S, Gabriel SB, Sallé FG, Gao J, Gardner J, Gastier-Foster JM, Gay CM, Gehlenborg N, Gerken M, Getz G, Gibb EA, Gibbs DL, Goparaju C, Graim K, Gross B, Guo G, Gupta M, Hasegawa S, Haussler D, Hayes DN, Heiman DI, Heins Z, Hmeljak J, Hoadley KA, Holt RA, Hoyle AP, Husain A, Hutter CM, Iype L, Jefferys SR, Jones SJM, Jones CD, Kanchi RS, Kasaian K, Kim J, Kindler H, Kondo N, Krausz T, Kundra R, Kuribayashi K, Kwiatkowski DJ, Ladanyi M, Lai PH, Laird PW, Lawrence MS, Lee D, Leraas KM, Lichtenberg TM, Lin P, Liu J, Liu W, Liu EM, Lolla L, Longatto-Filho A, Lu Y, Luketich J, Ma Y, Maglinte DT, Mallory D, Marra MA, Mayo M, Meier S, Melamed J, Meng S, Meyerson M, Mieczkowski PA, Mills GB, Moore RA, Moran C, Morris S, Mose LE, Mungall AJ, Mungall K, Nakano T, Naresh R, Newton Y, Noble MS, Ochoa A, Osmanbeyoglu H, Parker JS, Pass HI, Paulauskis J, Pennathur A, Pennell NA, Penny R, Perou CM, Pihl T, Ramirez NC, Rassl DM, Ravegnini G, Reid G, Reis RM, Reynolds SM, Rice D, Richards WG, Rintoul RC, Roach J, Robertson AG, Rusch V, Sadeghi S, Saksena G, Sanchez-Vega F, Sander C, Sato A, Scapulatempo-Neto C, Schein JE, Schultz N, Schumacher SE, Seiwert T, Sekido Y, Severson DT, Shelton C, Shelton T, Shen R, Sheridan R, Shi Y, Shih J, Shiraishi Y, Shmulevich I, Silveira HCS, Simons JV, Sipahimalani P, Skelly T, Sofia HJ, Soloway MG, Spellman P, Stewart C, Stuart J, Sun Q, Takeshita J, Tam A, Tan D, Tarnuzzer R, Tatsuno K, Taylor BS, Thiessen N, Thompson E, Thorsson V, Travis WD, Tsao A, Tse K, Tsujimura T, Valdivieso F, Van Den Berg DJ, van Zandwijk N, Veluvolu U, Viana LS, Voet D, Wan Y, Wang Z, Wang J, Weaver J, Weinstein JN, Weisenberger DJ, Wilkerson MD, Wise L, Wistuba I, Wong T, Wu Y, Yamamoto S, Yang L, Zauderer MG, Zenklusen JC, Zhang J, Zhang H, Zhang H, Zmuda E.

Author information

1
Department of Pathology and Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
2
Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
3
Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
4
The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.
5
Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
6
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland.
7
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
8
GenomeDx Biosciences, Vancouver, British Columbia, Canada.
9
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
10
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
11
Computational Systems Biology, Memorial Sloan Kettering Cancer Center, New York, New York.
12
Division of Cancer Biology, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan.
13
Genome Science Division, The University of Tokyo, Tokyo, Japan.
14
Department of Biomolecular Engineering and Center for Biomolecular Science and Engineering, University of California, Santa Cruz, Santa Cruz, California.
15
Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
16
Institute for Systems Biology, Seattle, Washington.
17
The University of Texas at Dallas, Richardson, Texas.
18
Division of Thoracic Surgery, The Lung Center and International Mesothelioma Program, Brigham and Women's Hospital, Boston, Massachusetts.
19
Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
20
Department of Pathology, Quebec Heart and Lung Institute, Quebec, Canada.
21
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
22
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
23
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
24
MESOPATH. Cancer Center Leon Berard, Lyon, France.
25
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
26
Department of Pathology, University of Chicago, Chicago, Illinois.
27
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil.
28
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
29
Department of Oncology, University of Cambridge, Cambridge, UK.
30
Department of Cardiothoracic Surgery, NYU Langone Medical Center, New York, New York.
31
Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center and Biological Sciences, Chicago, Illinois.
32
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
33
Division of Pulmonary Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
34
School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.
35
The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
36
National Cancer Institute, Bethesda, Maryland.
37
Department of Pathology and Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York. ladanyim@mskcc.org.

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.

PMID:
30322867
PMCID:
PMC6310008
[Available on 2019-12-01]
DOI:
10.1158/2159-8290.CD-18-0804

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center