Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium
Summary: 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 endometr...
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Elsevier
2018-08-01
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Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718311276 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kazuaki Suda Hirofumi Nakaoka Kosuke Yoshihara Tatsuya Ishiguro Ryo Tamura Yutaro Mori Kaoru Yamawaki Sosuke Adachi Tomoko Takahashi Hiroaki Kase Kenichi Tanaka Tadashi Yamamoto Teiichi Motoyama Ituro Inoue Takayuki Enomoto |
spellingShingle |
Kazuaki Suda Hirofumi Nakaoka Kosuke Yoshihara Tatsuya Ishiguro Ryo Tamura Yutaro Mori Kaoru Yamawaki Sosuke Adachi Tomoko Takahashi Hiroaki Kase Kenichi Tanaka Tadashi Yamamoto Teiichi Motoyama Ituro Inoue Takayuki Enomoto Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium Cell Reports |
author_facet |
Kazuaki Suda Hirofumi Nakaoka Kosuke Yoshihara Tatsuya Ishiguro Ryo Tamura Yutaro Mori Kaoru Yamawaki Sosuke Adachi Tomoko Takahashi Hiroaki Kase Kenichi Tanaka Tadashi Yamamoto Teiichi Motoyama Ituro Inoue Takayuki Enomoto |
author_sort |
Kazuaki Suda |
title |
Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium |
title_short |
Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium |
title_full |
Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium |
title_fullStr |
Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium |
title_full_unstemmed |
Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal Endometrium |
title_sort |
clonal expansion and diversification of cancer-associated mutations in endometriosis and normal endometrium |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-08-01 |
description |
Summary: 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. : Suda et al. identify numerous cancer-associated mutations in epithelial cells from ovarian endometriosis and normal endometrium. They describe a heterogeneous and mosaic-like uterine endometrial epithelium, shaped by endometrial glands with distinct somatic mutations. They suggest clonal expansion of epithelial cells with cancer-associated mutations leads to the development of endometriosis. Keywords: endometriosis, uterine endometrium, ovarian cancer, epithelial cell, endometrial gland, next-generation sequencing, multiregional sequencing, somatic mutation, clonal evolution, genomic heterogeneity |
url |
http://www.sciencedirect.com/science/article/pii/S2211124718311276 |
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doaj-4c1c006280d94a18b28df391fffb677c2020-11-25T01:11:33ZengElsevierCell Reports2211-12472018-08-0124717771789Clonal Expansion and Diversification of Cancer-Associated Mutations in Endometriosis and Normal EndometriumKazuaki Suda0Hirofumi Nakaoka1Kosuke Yoshihara2Tatsuya Ishiguro3Ryo Tamura4Yutaro Mori5Kaoru Yamawaki6Sosuke Adachi7Tomoko Takahashi8Hiroaki Kase9Kenichi Tanaka10Tadashi Yamamoto11Teiichi Motoyama12Ituro Inoue13Takayuki Enomoto14Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, JapanDivision of Human Genetics, National Institute of Genetics, Mishima 411-8540, JapanDepartment of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Corresponding authorDepartment of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, JapanDepartment of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, JapanDepartment of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, JapanDepartment of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, JapanDepartment of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, JapanCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, JapanDepartment of Obstetrics and Gynecology, Nagaoka Chuo General Hospital, Nagaoka 940-8653, JapanNiigata Medical Center Hospital, Niigata 950-2022, JapanCOI-s Biofluid Biomarker Center, Institute of Research Collaboration and Promotion, Niigata University, Niigata 950-2181, JapanDepartment of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, JapanDivision of Human Genetics, National Institute of Genetics, Mishima 411-8540, Japan; Corresponding authorDepartment of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Corresponding authorSummary: 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. : Suda et al. identify numerous cancer-associated mutations in epithelial cells from ovarian endometriosis and normal endometrium. They describe a heterogeneous and mosaic-like uterine endometrial epithelium, shaped by endometrial glands with distinct somatic mutations. They suggest clonal expansion of epithelial cells with cancer-associated mutations leads to the development of endometriosis. Keywords: endometriosis, uterine endometrium, ovarian cancer, epithelial cell, endometrial gland, next-generation sequencing, multiregional sequencing, somatic mutation, clonal evolution, genomic heterogeneityhttp://www.sciencedirect.com/science/article/pii/S2211124718311276 |