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 U.
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.
AU - Rusch, Valerie W.
AU - Rintoul, Robert C.
AU - Pass, Harvey I.
AU - Kindler, Hedy
AU - Zauderer, Marjorie G.
AU - Kwiatkowski, David J.
AU - Bueno, Raphael
AU - Tsao, Anne S.
AU - Creaney, Jenette
AU - Lichtenberg, Tara
AU - Leraas, Kristen
AU - Bowen, Jay
AU - Baylin, Stephen B.
AU - Cope, Leslie
AU - Seiwert, Tanguy
N1 - Funding Information:
L.R. Chirieac has received remuneration for medicolegal work related to mesothelioma. V.W. Rusch reports receiving a commercial research grant from Genentech and is a consultant/advisory board member for BMS. H. Pass reports receiving a commercial research grant from Genentech. M.G. Zauderer is a member of the Board of Directors of the Mesothelioma Applied Research Foundation, reports receiving commercial research grants from Bristol-Meyers Squibb and Millennium, and is a consultant/advisory board member for AstraZeneca, Sellas Life Science, and Epizyme. D.J. Kwiatkowski is a consultant/advisory board member for Novartis. R. Bueno has ownership interest (including stock, patents, etc.) in Navigation Sciences. A.D. Cherniack reports receiving commercial research support from Bayer. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
We thank Drs. Elaine Mardis and Matthew Meyerson for invaluable feedback and Dr. Lee Spraggon for helpful comments and assistance with figures. This work was supported by the following grants from the USA National Institutes of Health: U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, P30 CA016672, and P30 CA008748. Whole-exome sequencing and analysis was funded by the British Lung Foundation grant APG11-7 (“The genomic architecture of mesothelioma”). Publication charges were funded by the Memorial Sloan Kettering Mesothelioma Program Fund.
Publisher Copyright:
© 2018 AACR.
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.
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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 -