Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity.

Humans Mesothelioma, Malignant / genetics Mesothelioma / genetics Multiomics Pleural Neoplasms / genetics Lung Neoplasms / pathology Biomarkers, Tumor / genetics

Journal

Nature genetics

ISSN: 1546-1718

Titre abrégé: Nat Genet

Pays: United States

ID NLM: 9216904

Informations de publication

Date de publication:
04 2023

Historique:

received: 25 12 2021

accepted: 26 01 2023

medline: 17 4 2023

pubmed: 18 3 2023

entrez: 17 3 2023

Statut: ppublish

Résumé

Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that-in the case of the interdependent tumor cell morphology and adapted immune response-reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.

Identifiants

DOI: 10.1038/s41588-023-01321-1 PMID: 36928603 PMC: PMC10101853

pubmed: 36928603

doi: 10.1038/s41588-023-01321-1

pii: 10.1038/s41588-023-01321-1

pmc: PMC10101853

doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

607-618

Informations de copyright

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