Integrative Molecular Characterization of Malignant Pleural Mesothelioma

Genomic and clinical characteristics of TCGA MPM cohort, highlighting clinical and molecular features, a hypermutated case, mutational spectra, and a comparison of significantly mutated genes.

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.

Citation

The Cancer Genome Atlas Research Network (incl. N Gehlenborg). “Integrative Molecular Characterization of Malignant Pleural Mesothelioma”, Cancer Discovery 8(12):1548-1565 (2018). doi:10.1158/2159-8290.CD-18-0804