Dissecting the Origin of Heterogeneity in Uterine and Ovarian Carcinosarcomas.
Fiche publication
Date publication
mai 2023
Journal
Cancer research communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ARNOULD Laurent
Tous les auteurs :
Sertier AS, Ferrari A, Pommier RM, Treilleux I, Boyault S, Devouassoux-Shisheboran M, Kielbassa J, Thomas E, Tonon L, Le Texier V, Charreton A, Morel AP, Floquet A, Joly F, Berton-Rigaud D, Ferron G, Arnould L, Croce S, Bataillon G, Saintigny P, Mery-Lamarche E, Sagan C, Senaratne AP, Gut IG, Calvo F, Viari A, Ouzounova M, Ray-Coquard I, Puisieux A
Lien Pubmed
Résumé
Gynecologic carcinosarcomas (CS) are biphasic neoplasms composed of carcinomatous (C) and sarcomatous (S) malignant components. Because of their rarity and histologic complexity, genetic and functional studies on CS are scarce and the mechanisms of initiation and development remain largely unknown. Whole-genome analysis of the C and S components reveals shared genomic alterations, thus emphasizing the clonal evolution of CS. Reconstructions of the evolutionary history of each tumor further reveal that C and S samples are composed of both ancestral cell populations and component-specific subclones, supporting a common origin followed by distinct evolutionary trajectories. However, while we do not find any recurrent genomic features associated with phenotypic divergence, transcriptomic and methylome analyses identify a common mechanism across the cohort, the epithelial-to-mesenchymal transition (EMT), suggesting a role for nongenetic factors in inflicting changes to cellular fate. Altogether, these data accredit the hypothesis that CS tumors are driven by both clonal evolution and transcriptomic reprogramming, essential for susceptibility to transdifferentiation upon encountering environmental cues, thus linking CS heterogeneity to genetic, transcriptomic, and epigenetic influences.
Mots clés
Humans, Female, Carcinosarcoma, genetics, Ovarian Neoplasms, genetics, Sarcoma
Référence
Cancer Res Commun. 2023 05;3(5):830-841