Back to Search Start Over

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

Authors :
Suda K
Nakaoka H
Yoshihara K
Ishiguro T
Tamura R
Mori Y
Yamawaki K
Adachi S
Takahashi T
Kase H
Tanaka K
Yamamoto T
Motoyama T
Inoue I
Enomoto T
Source :
Cell reports [Cell Rep] 2018 Aug 14; Vol. 24 (7), pp. 1777-1789.
Publication Year :
2018

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.<br /> (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
2211-1247
Volume :
24
Issue :
7
Database :
MEDLINE
Journal :
Cell reports
Publication Type :
Academic Journal
Accession number :
30110635
Full Text :
https://doi.org/10.1016/j.celrep.2018.07.037