論文

査読有り 国際誌
2021年1月

Genome-wide mutation analysis in precancerous lesions of endometrial carcinoma

JOURNAL OF PATHOLOGY
  • Lihong Li
  • ,
  • Pinli Yue
  • ,
  • Qianqian Song
  • ,
  • Ting-Tai Yen
  • ,
  • Shiho Asaka
  • ,
  • Tian-Li Wang
  • ,
  • Anna L. Beavis
  • ,
  • Amanda N. Fader
  • ,
  • Yuchen Jiao
  • ,
  • Guangwen Yuan
  • ,
  • Ie-Ming Shih
  • ,
  • Yan Song

253
1
開始ページ
119
終了ページ
128
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/path.5566
出版者・発行元
WILEY

Clinicopathological evidence supports endometrial atypical hyperplasia (AH) or endometrial intraepithelial neoplasia as the precursor of uterine endometrioid carcinoma (EC), the most common gynecologic malignancy. However, the pathogenic progression from AH to EC remains unclear. Here, we employed whole-exome sequencing to identify somatic mutations and copy number changes in micro-dissected lesions from 30 pairs of newly diagnosed AH and EC. We found that all but one pair of AHs shared the same DNA mismatch repair status as their corresponding ECs. The percentage of common mutations between AH lesions and corresponding ECs varied significantly, ranging from 0.1% to 82%. Microsatellite stable AHs had fewer cancer driver mutations than ECs (5 versus 7, p = 0.017), but among microsatellite unstable AHs and ECs there was no difference in mutational numbers (36 versus 38, p = 0.65). As compared to AH specimens, 19 (79%) of 24 microsatellite stable EC tumors gained new cancer driver mutations, most of which involved PTEN, ARID1A, PIK3CA, CTNNB1, or CHD4. Our results suggest that some AH lesions are the immediate precursor of ECs, and progression depends on acquisition of additional cancer driver mutations. However, a complex clonal relationship between AH and EC can also be appreciated, as in some cases both lesions diverge very early or arise independently, thus co-developing with distinct genetic trajectories. Our genome-wide profile of mutations in AH and EC shines new light on the molecular landscape of tumor progression. (c) 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Web of Science ® 被引用回数 : 11

リンク情報
DOI
https://doi.org/10.1002/path.5566
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33016334
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000588833300001&DestApp=WOS_CPL
ID情報
  • DOI : 10.1002/path.5566
  • ISSN : 0022-3417
  • eISSN : 1096-9896
  • PubMed ID : 33016334
  • Web of Science ID : WOS:000588833300001

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