Genomic evolution of ovarian endometrioid and clear-cell carcinomas

Ovarian endometrioid carcinoma (OEC) and ovarian clear-cell carcinoma (OCCC) are distinct histological subtypes of ovarian cancer that share a common association with endometriosis but diverge in clinical features such as responses to therapy or microsatellite instability. Advances in next-generation sequencing have deepened our understanding of the clonal architecture and evolutionary dynamics of these subtypes. Specifically, the application of whole-genome, whole-exome, and RNA sequencing or single-cell and spatial transcriptomes has provided a clearer picture of the evolutionary trajectories of OEC and OCCC from normal endometrium to invasive malignancies via endometriotic lesions. Emerging data point to characteristic mutations in AT-rich interaction domain 1A (ARID1A), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), KRAS proto-oncogene, GTPase (KRAS), and catenin beta 1 (CTNNB1), as well as alterations in chromatin remodeling complexes and metabolic pathways. Importantly, recent efforts have underscored the tumor microenvironment heterogeneity that may predict therapeutic response and prognosis. In this review, we summarize the current knowledge on the genomic evolution of OEC and OCCC, highlight the role of key genomic alterations, discuss the influence of the tumor microenvironment, and explore potential avenues for targeted treatment.