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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                    <jats:p>See related commentary by Aggarwal and Albelda, p. 1508.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 1494<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-18-0804","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T09:10:08Z","timestamp":1539594608000},"page":"1548-1565","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":542,"title":["Integrative Molecular Characterization of Malignant Pleural Mesothelioma"],"prefix":"10.1158","volume":"8","author":[{"given":"Julija","family":"Hmeljak","sequence":"first","affiliation":[{"name":"1Department of Pathology and Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York."}]},{"given":"Francisco","family":"Sanchez-Vega","sequence":"additional","affiliation":[{"name":"2Marie-Jos\u00e9e and Henry R. 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