Mutation and methylation profiles of ectopic and eutopic endometrial tissues.
Mutation and methylation profiles of ectopic and eutopic endometrial tissues.
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DOI：
10.1002/path.5778
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发表时间：
2021-12
期刊：
影响因子：
--
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中科院分区：
文献类型：
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子宫腺肌病和腹膜子宫内膜异位症是常见的妇科疾病，其特征是正常的子宫内膜分别位于子宫肌层和腹膜表面。推测这两种异位病变都起源于子宫在位内膜，子宫在位内膜由上皮和基质组成，但这两种不同的组织类型如何在异位部位共同进化仍不清楚。在此，我们分析了成对子宫腺肌病、腹膜子宫内膜异位症和子宫内膜中显微解剖上皮和间质的外显子组突变和整体甲基化，以探讨它们之间的关系。体细胞突变及其等位基因频率的分析表明，单克隆发展不仅在上皮细胞，而且在子宫腺肌病和腹膜子宫内膜异位症的间质。我们初步的系统发育研究表明，异位和在位子宫内膜的上皮和间质来源于相同的上皮-间质祖细胞。虽然患者特异性甲基化景观是明显的，但子宫腺肌病上皮和间质可以与正常的在位子宫内膜区分开来，并且表观遗传学上不太均匀。总之，子宫内膜间质，像它的上皮对应物，可以是克隆的，异位和在位子宫内膜遵循不同的进化轨迹。我们的数据也保证了未来的研究子宫内膜间质的作用，在子宫内膜相关疾病的病理生物学。
Adenomyosis and peritoneal endometriosis are common gynecologic lesions; they are characterized by aberrant locations of normal-appearing endometrium in myometrium and peritoneal surface, respectively. Both ectopic lesions are speculated to originate from uterine eutopic endometrium, which is composed of epithelium and stroma, but how these two different tissue types co-evolve in ectopic locations remain unclear. Here, we analyzed exome-wide mutations and global methylation in microdissected epithelium and stroma separately in paired adenomyosis, peritoneal endometriosis, and endometrium to investigate their relationship. Analyses of somatic mutations and their allele frequencies indicate mono-clonal development not only in epithelium but also in the stroma of adenomyosis and peritoneal endometriosis. Our preliminary phylogenetic study suggests a plausible clonal derivation in epithelium and stroma of both ectopic and eutopic endometrium from the same founder epithelium-stroma progenitor cells. While a patient-specific methylation landscape is evident, adenomyosis epithelium and stroma can be distinguished from normal-appearing eutopic endometrium and epigenetically less homogenous. In summary, endometrial stroma, like its epithelial counterpart, could be clonal and both ectopic and eutopic endometrium following divergent evolutionary trajectories. Our data also warrant future investigations into the role of endometrial stroma in the pathobiology of endometrium-related disorders.
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DOI：
10.1056/nejmoa1614814
发表时间：
2017-05-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Anglesio MS;Papadopoulos N;Ayhan A;Nazeran TM;Noë M;Horlings HM;Lum A;Jones S;Senz J;Seckin T;Ho J;Wu RC;Lac V;Ogawa H;Tessier-Cloutier B;Alhassan R;Wang A;Wang Y;Cohen JD;Wong F;Hasanovic A;Orr N;Zhang M;Popoli M;McMahon W;Wood LD;Mattox A;Allaire C;Segars J;Williams C;Tomasetti C;Boyd N;Kinzler KW;Gilks CB;Diaz L;Wang TL;Vogelstein B;Yong PJ;Huntsman DG;Shih IM
通讯作者：
Shih IM
DOI：
10.1016/j.ejogrb.2011.03.003
发表时间：
2011-08-01
影响因子：
2.6
作者：
Larsen, S. B.;Lundorf, E.;Dueholm, M.
通讯作者：
Dueholm, M.
影响因子：
64.8
作者：
Moore, Luiza;Leongamornlert, Daniel;Stratton, Michael R.
通讯作者：
Stratton, Michael R.
DOI：
10.1016/0002-9378(72)90781-8
发表时间：
1972-01-01
影响因子：
9.8
作者：
BIRD, CC;MCELIN, TW;MANALOES.P
通讯作者：
MANALOES.P
影响因子：
12.3
作者：
Horvath S
通讯作者：
Horvath S