Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium

TLDR

"Both endometriotic and normal epithelium contain numerous somatic mutations in cancer‑associated genes, with KRAS mutations showing higher allele frequencies and chromosomal imbalances in endometriotic tissue; each single endometrial gland harbors distinct mutations, indicating extensive heterogeneity, and the elevated mutation burden in ectopic endometriosis implies retrograde flow of mutated endometrial cells conferring selective growth advantage." Other: [Findings, Other] line: "Remarkable increases in MAF of mutations in cancer-associated genes in endometriotic epithelium suggest retrograde flow of endometrial cells already harboring cancer-associated mutations, with selective advantages at ectopic sites, leading to the development of endometriosis.Graphical abstract". Also maybe other meta? There's "Graphical abstract" but not needed. So other: maybe summarise that.

Abstract

Highlights•Endometriosis and uterine endometrium exhibit cancer-associated somatic mutations•Clonal expansion of epithelial cells with cancer-associated mutations in endometriosis•Genomic architecture of epithelial cells in uterine endometrium is heterogeneous•Single endometrial glands carry distinct mutations in cancer-associated genesSummaryEndometriosis is characterized by ectopic endometrial-like epithelium and stroma, of which molecular characteristics remain to be fully elucidated. We sequenced 107 ovarian endometriotic and 82 normal uterine endometrial epithelium samples isolated by laser microdissection. In both endometriotic and normal epithelium samples, numerous somatic mutations were identified within genes frequently mutated in endometriosis-associated ovarian cancers. KRAS is frequently mutated in endometriotic epithelium, with a higher mutant allele frequency (MAF) accompanied by arm-level allelic imbalances. Analyses of MAF, combined with multiregional sequencing, illuminated spatiotemporal evolution of the endometriosis and uterine endometrium genomes. We sequenced 109 single endometrial glands and found that each gland carried distinct cancer-associated mutations, demonstrating the heterogeneity of the genomic architecture of endometrial epithelium. Remarkable increases in MAF of mutations in cancer-associated genes in endometriotic epithelium suggest retrograde flow of endometrial cells already harboring cancer-associated mutations, with selective advantages at ectopic sites, leading to the development of endometriosis.Graphical abstract