Integrative molecular characterization of malignant pleural mesothelioma

TCGA Research Network

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 expresssion of the immune-checkpoint gene VISTA in epithelioid MPM.

Original languageEnglish (US)
Pages (from-to)1549-1565
Number of pages17
JournalCancer Discovery
Volume8
Issue number12
DOIs
StatePublished - Dec 1 2018

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Loss of Heterozygosity
Histology
Mutation
Immunotherapy
Genes
Malignant Mesothelioma
Neoplasms
Thorax
Therapeutics

ASJC Scopus subject areas

  • Oncology

Cite this

Integrative molecular characterization of malignant pleural mesothelioma. / TCGA Research Network.

In: Cancer Discovery, Vol. 8, No. 12, 01.12.2018, p. 1549-1565.

Research output: Contribution to journalArticle

TCGA Research Network. / Integrative molecular characterization of malignant pleural mesothelioma. In: Cancer Discovery. 2018 ; Vol. 8, No. 12. pp. 1549-1565.
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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 expresssion of the immune-checkpoint gene VISTA in epithelioid MPM.",
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