测序技术的进步揭示了正常组织中突变特征和体细胞驱动突变的高度多样化。正常组织的突变积累速率不同，在肝脏中，每个细胞每年平均发生11个突变，而在膀胱中，每个细胞每年平均发生1879个突变。此外，一些正常组织中大部分细胞的表型正常，但却携带驱动突变。在食道中，大多数细胞携带驱动突变。个体组织的增殖和突变速率、独特的致突变刺激和局部组织结构，共同造成了这种高度多样化的背景，使得突变的功能特性很难被解析。特别是，我们对正常组织体细胞突变与肿瘤发生或未来癌症风险之间的关系了解甚少。在这里，我们描述了实体和腔体器官中的突变特征和体细胞驱动突变，并突出了以组织特异性方式展现的独特特点，同时试图描述可以带来肿瘤起始中这些驱动突变作用基本统一理论的共同特点。我们还讨论了可以为未来研究提供参考的新发现。©2023.作者。

Advances in sequencing have revealed a highly variegated landscape of mutational signatures and somatic driver mutations in a range of normal tissues. Normal tissues accumulate mutations at varying rates ranging from 11 per cell per year in the liver, to 1879 per cell per year in the bladder. In addition, some normal tissues are also comprised of a large proportion of cells which possess driver mutations while appearing phenotypically normal, as in the oesophagus where a majority of cells harbour driver mutations. Individual tissue proliferation and mutation rate, unique mutagenic stimuli, and local tissue architecture contribute to this highly variegated landscape which confounds the functional characterization of driver mutations found in normal tissue. In particular, our understanding of the relationship between normal tissue somatic mutations and tumour initiation or future cancer risk remains poor. Here, we describe the mutational signatures and somatic driver mutations in solid and hollow viscus organs, highlighting unique characteristics in a tissue-specific manner, while simultaneously seeking to describe commonalities which can bring forward a basic unified theory on the role of these driver mutations in tumour initiation. We discuss novel findings which can be used to inform future research in this field.© 2023. The Author(s).