| Literature DB >> 30322867 |
Julija Hmeljak1, Francisco Sanchez-Vega2, Katherine A Hoadley3, Juliann Shih4, Chip Stewart3, David Heiman3, Patrick Tarpey5, Ludmila Danilova6, Esther Drill7, Ewan A Gibb8, Reanne Bowlby9, Rupa Kanchi10, Hatice U Osmanbeyoglu11, Yoshitaka Sekido12, Jumpei Takeshita13, Yulia Newton14, Kiley Graim14, Manaswi Gupta4, Carl M Gay15, Lixia Diao10, David L Gibbs16, Vesteinn Thorsson16, Lisa Iype16, Havish Kantheti17, David T Severson18, Gloria Ravegnini19, Patrice Desmeules20, Achim A Jungbluth21, William D Travis21, Sanja Dacic22, Lucian R Chirieac23, Françoise Galateau-Sallé24, Junya Fujimoto25, Aliya N Husain26, Henrique C Silveira27, Valerie W Rusch28, Robert C Rintoul29, Harvey Pass30, Hedy Kindler31, Marjorie G Zauderer32, David J Kwiatkowski33, Raphael Bueno18, Anne S Tsao15, Jenette Creaney34, Tara Lichtenberg35, Kristen Leraas35, Jay Bowen35, Ina Felau36, Jean Claude Zenklusen36, Rehan Akbani10, Andrew D Cherniack4, Lauren A Byers18, Michael S Noble4, Jonathan A Fletcher22, A Gordon Robertson9, Ronglai Shen7, Hiroyuki Aburatani13, Bruce W Robinson34, Peter Campbell5, Marc Ladanyi37.
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. ©2018 American Association for Cancer Research.Entities:
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Year: 2018 PMID： 30322867 PMCID： PMC6310008 DOI： 10.1158/2159-8290.CD-18-0804
Source DB: PubMed Journal: Cancer Discov ISSN： 2159-8274 Impact factor: 39.397