Early Detection Research Network

Integrative Molecular Characterization of Malignant Pleural Mesothelioma.

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 <i>BAP1</i> alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with <i>TP53</i> and <i>SETDB1</i> mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene <i>VISTA</i> 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 <i>TP53</i> and <i>SETDB1</i> mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene <i>VISTA</i> in epithelioid MPM.<i>See related commentary by Aggarwal and Albelda, p. 1508</i>.<i>This article is highlighted in the In This Issue feature, p. 1494</i>.

Aburatani H, Akbani R, Bowen J, Bowlby R, Bueno R, Byers LA, Campbell P, Cherniack AD, Chirieac LR, Creaney J, Dacic S, Danilova L, Desmeules P, Diao L, Drill E, Felau I, Fletcher JA, Fujimoto J, Galateau-Sallé F, Gay CM, Gibb EA, Gibbs DL, Graim K, Gupta M, Heiman D, Hmeljak J, Hoadley KA, Husain AN, Iype L, Jungbluth AA, Kanchi R, Kantheti H, Kindler H, Kwiatkowski DJ, Ladanyi M, Leraas K, Lichtenberg T, Newton Y, Noble MS, Osmanbeyoglu HU, Pass H, Ravegnini G, Rintoul RC, Robertson AG, Robinson BW, Rusch VW, Sanchez-Vega F, Sekido Y, Severson DT, Shen R, Shih J, Silveira HC, Stewart C, Takeshita J, Tarpey P, Thorsson V, Travis WD, Tsao AS, Zauderer MG, Zenklusen JC

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Cancer Discov, 2018, 8 (12)

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