SCIENCE@home

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

K. Suda,H. Nakaoka,K. Yoshihara,T. Ishiguro,Ryo Tamura,Yutaro Mori,Kaoru Yamawaki,S. Adachi,Tomoko Takahashi,H. Kase,Kenichi Tanaka,Tadashi Yamamoto,T. Motoyama,I. Inoue,T. Enomoto

Published 2018 in Cell Reports

ABSTRACT

Endometriosis 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.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-69 of 69 references · Page 1 of 1

CITED BY

Showing 1-100 of 366 citing papers · Page 1 of 4

1234
Next