crc-22-0520-s10.pdf (2.07 MB)
Figure S7 from Dissecting the origin of heterogeneity in uterine and ovarian carcinosarcomas
journal contributionposted on 2023-04-26, 14:21 authored by Anne-Sophie Sertier, Anthony Ferrari, Roxane M. Pommier, Isabelle Treilleux, Sandrine Boyault, Mojgan Devouassoux-Shisheboran, Janice Kielbassa, Emilie Thomas, Laurie Tonon, Vincent Le Texier, Amandine Charreton, Anne-Pierre Morel, Anne Floquet, Florence Joly, Dominique Berton-Rigaud, Gwenaël Ferron, Laurent Arnould, Sabrina Croce, Guillaume Bataillon, Pierre Saintigny, Eliane Mery-Lamarche, Christine Sagan, Aruni P. Senaratne, Ivo G. Gut, Fabien Calvo, Alain Viari, Maria Ouzounova, Isabelle Ray-Coquard, Alain Puisieux
Alteration of chromatin remodeling genes in uterine and ovarian CS.
ARTICLE ABSTRACTGynecologic carcinosarcomas (CS), are biphasic neoplasms composed of carcinomatous (C) epithelial and sarcomatous (S) malignant components. Due to their rarity and histological 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 sub-clones, 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 non-genetic 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.