小柯机器人

近日，英国威康桑格研究所Michael R. Stratton课题组绘制出正常人类子宫内膜上皮的突变图谱取得。2020年4月22日，《自然》杂志在线发表了相关论文。

使用全基因组测序，研究人员发现正常人子宫内膜腺体是具有总突变负担的克隆细胞群体，其总突变负担每年以约29个碱基的替换量增加，并且比子宫内膜癌的突变率低许多倍。

正常的子宫内膜腺癌经常携带癌基因的“驱动基因”突变，其负担随着年龄的增长而增加，随着胎次的减少而降低。具有驱动基因的细胞克隆通常起源于生命的最初几十年，随后逐渐在子宫内膜的上皮内层定植。

这些研究结果表明，正常组织之间的突变情况存在显著差异（可能是由于其结构和生理差异而形成的），并表明导致子宫内膜癌的肿瘤改变过程是在人生早期开始的。

据介绍，所有正常的体细胞都被认为具有突变，但是对正常细胞中体细胞突变的发生率、模式、原因和后果的了解是有限的。子宫内膜在一生中具有多种生理状态，并被形成腺体的上皮所包围。

附：英文原文

Title: The mutational landscape of normal human endometrial epithelium

Author: Luiza Moore, Daniel Leongamornlert, Tim H. H. Coorens, Mathijs A. Sanders, Peter Ellis, Stefan C. Dentro, Kevin J. Dawson, Tim Butler, Raheleh Rahbari, Thomas J. Mitchell, Francesco Maura, Jyoti Nangalia, Patrick S. Tarpey, Simon F. Brunner, Henry Lee-Six, Yvette Hooks, Sarah Moody, Krishnaa T. Mahbubani, Mercedes Jimenez-Linan, Jan J. Brosens, Christine A. Iacobuzio-Donahue, Inigo Martincorena, Kourosh Saeb-Parsy, Peter J. Campbell, Michael R. Stratton

Issue&Volume: 2020-04-22

Abstract: All normal somatic cells are thought to acquire mutations, but understanding of the rates, patterns, causes and consequences of somatic mutations in normal cells is limited. The uterine endometrium adopts multiple physiological states over a lifetime and is lined by a gland-forming epithelium1,2. Here, using whole-genome sequencing, we show that normal human endometrial glands are clonal cell populations with total mutation burdens that increase at about 29 base substitutions per year and that are many-fold lower than those of endometrial cancers. Normal endometrial glands frequently carry ‘driver’ mutations in cancer genes, the burden of which increases with age and decreases with parity. Cell clones with drivers often originate during the first decades of life and subsequently progressively colonize the epithelial lining of the endometrium. Our results show that mutational landscapes differ markedly between normal tissues—perhaps shaped by differences in their structure and physiology—and indicate that the procession of neoplastic change that leads to endometrial cancer is initiated early in life.

DOI: 10.1038/s41586-020-2214-z

Source: https://www.nature.com/articles/s41586-020-2214-z

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