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The landscape of somatic mutation in normal colorectal epithelial cells

机译：正常结直肠上皮细胞中体细胞突变的情况

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The colorectal adenoma-carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic changes and consequent clonal expansions that lead to cancer(1). 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.
机译：大肠腺瘤-癌序列提供了一个范式框架，用于了解连续的体细胞遗传变化和随之而来的导致癌症的克隆扩增（1）。但是，对于大多数癌症类型，我们对大肠肿瘤改变最早阶段（可能发生在形态正常的组织中）的理解相对有限。在这里，我们使用全基因组测序来分析来自42个个体的数百个正常隐窝。揭示了多个突变过程的特征；其中一些无处不在并且是连续的，而其他仅在某些人，某些隐窝或生命的某些时期被发现。在中年人的正常结直肠隐窝中大约1％存在可能的驱动程序突变，这表明腺瘤和癌是在形态学正常的结直肠上皮细胞上普遍发生的肿瘤改变过程的罕见结果。相对于正常细胞，结直肠癌表现出显着增加的突变负担。对正常结直肠细胞进行测序可提供有关癌症基因组和克隆进化的定量见解。

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