論文

国際誌
2022年2月17日

Spatiotemporal dynamics of clonal selection and diversification in normal endometrial epithelium.

Nature communications
  • Manako Yamaguchi
  • Hirofumi Nakaoka
  • Kazuaki Suda
  • Kosuke Yoshihara
  • Tatsuya Ishiguro
  • Nozomi Yachida
  • Kyota Saito
  • Haruka Ueda
  • Kentaro Sugino
  • Yutaro Mori
  • Kaoru Yamawaki
  • Ryo Tamura
  • Sundaramoorthy Revathidevi
  • Teiichi Motoyama
  • Kazuki Tainaka
  • Roel G W Verhaak
  • Ituro Inoue
  • Takayuki Enomoto
  • 全て表示

13
1
開始ページ
943
終了ページ
943
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41467-022-28568-2

It has become evident that somatic mutations in cancer-associated genes accumulate in the normal endometrium, but spatiotemporal understanding of the evolution and expansion of mutant clones is limited. To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-associated genes in the normal endometrium, we sequence 1311 endometrial glands from 37 women. By collecting endometrial glands from different parts of the endometrium, we show that multiple glands with the same somatic mutations occupy substantial areas of the endometrium. We demonstrate that "rhizome structures", in which the basal glands run horizontally along the muscular layer and multiple vertical glands rise from the basal gland, originate from the same ancestral clone. Moreover, mutant clones detected in the vertical glands diversify by acquiring additional mutations. These results suggest that clonal expansions through the rhizome structures are involved in the mechanism by which mutant clones extend their territories. Furthermore, we show clonal expansions and copy neutral loss-of-heterozygosity events occur early in life, suggesting such events can be tolerated many years in the normal endometrium. Our results of the evolutionary dynamics of mutant clones in the human endometrium will lead to a better understanding of the mechanisms of endometrial regeneration during the menstrual cycle and the development of therapies for the prevention and treatment of endometrium-related diseases.

リンク情報
DOI
https://doi.org/10.1038/s41467-022-28568-2
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35177608
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8854701
ID情報
  • DOI : 10.1038/s41467-022-28568-2
  • PubMed ID : 35177608
  • PubMed Central 記事ID : PMC8854701

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