Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity
Menée à partir de données cliniques portant sur 123 patients atteints d'un mésothéliome pleural malin (âge médian : 67,5 ans ; 73 % d'hommes) et menée à partir de l'analyse multiomique de pièces de résection, cette étude identifie des caractéristiques morphologiques et moléculaires (ploïdie, morphologie cellulaire, réponse immunitaire adaptative et profil de méthylation du dinucléotide CpG) favorisant l'hétérogénéité intertumorale
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.
Nature Genetics , article en libre accès, 2023