科學家繪製正常結直腸上皮細胞體細胞突變圖譜
作者：
小柯機器人發布時間：2019/10/24 15:24:38
英國維康桑格研究所Michael R. Stratton小組繪製了正常結直腸上皮細胞的體細胞突變圖譜。這一成果發表在2019年10月24日出版的《自然》雜誌上。
研究人員使用全基因組測序分析來自42名個體的數百個正常隱窩。揭示了多個突變過程的特徵；其中一些普遍存在並且是連續的，而其他僅在某些人、某些隱窩或生命的某些時期被發現。在中年人的正常結直腸隱窩中大約1％存在可能的驅動程序突變，這表明，腺瘤和腫瘤是，在形態學正常結直腸上皮細胞上普遍發生的腫瘤改變過程的罕見結果。相對於正常細胞，結直腸癌表現出顯著增加的突變負擔。對正常結直腸細胞進行測序可提供有關癌症基因組和克隆進化的定量見解。
據介紹，結直腸腺瘤到腫瘤的變化提供了一個範式框架，可用於理解連續的體細胞遺傳變化和隨之而來的導致癌症的克隆擴增。但是，對於大多數癌症類型，人們對結直腸腫瘤改變最早階段（可能發生在形態正常的組織中）的理解相對有限。
附：英文原文
Title:The landscape of somatic mutation in normal colorectal epithelial cells
Author:Henry Lee-Six, Sigurgeir Olafsson, Peter Ellis, Robert J. Osborne, Mathijs A. Sanders, Luiza Moore, Nikitas Georgakopoulos, Franco Torrente, Ayesha Noorani, Martin Goddard, Philip Robinson, Tim H. H. Coorens, Laura O』Neill, Christopher Alder, Jingwei Wang, Rebecca C. Fitzgerald, Matthias Zilbauer, Nicholas Coleman, Kourosh Saeb-Parsy, Inigo Martincorena, Peter J. Campbell & Michael R. Stratton
Issue&Volume:Volume 574 Issue 7779
Abstract:
The colorectal adenoma–carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic changes and consequent clonal expansions that lead to cancer1. However, our understanding of the earliest phases of colorectal neoplastic changes—which may occur in morphologically normal tissue—is comparatively limited, as for most cancer types. Here we use whole-genome sequencing to analyse hundreds of normal crypts from 42 individuals. Signatures of multiple mutational processes were revealed; some of these were ubiquitous and continuous, whereas others were only found in some individuals, in some crypts or during certain periods of life. Probable driver mutations were present in around 1% of normal colorectal crypts in middle-aged individuals, indicating that adenomas and carcinomas are rare outcomes of a pervasive process of neoplastic change across morphologically normal colorectal epithelium. Colorectal cancers exhibit substantially increased mutational burdens relative to normal cells. Sequencing normal colorectal cells provides quantitative insights into the genomic and clonal evolution of cancer.
DOI:10.1038/s41586-019-1672-7