Genome-wide mutation analysis in precancerous lesions of endometrial carcinoma

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*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

27 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)119-128
頁數10
期刊Journal of Pathology
253
發行號1
DOIs
出版狀態已出版 - 01 2021
對外發佈

文獻附註

Publisher Copyright:
© 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

指紋

深入研究「Genome-wide mutation analysis in precancerous lesions of endometrial carcinoma」主題。共同形成了獨特的指紋。

引用此