APOBEC基因突变特征SBS2和SBS13在许多人类癌症类型中很常见。但是，对于其刺激、从正常到癌细胞进展发生的时间以及负责APOBEC酶仍存在不完全的理解。在这里，我们对39名个体的小肠上皮隐窝的342个微切割标本进行了整个基因组测序，并发现SBS2/SBS13突变在17%的隐窝中存在，比大多数其他正常组织更常见。带有SBS2/SBS13的隐窝常常有没有SBS2/SBS13的相邻隐窝，提示SBS2/SBS13的根本原因是细胞内在的。APOBEC诱变在人类寿命中以间歇方式发生，包括在年幼的儿童身上。在小肠上皮细胞中，APOBEC1 mRNA水平非常高，在大肠上皮及其他组织中较低。结果表明，小肠中SBS2/SBS13的高水平是APOBEC1履行其编辑APOB mRNA的生理功能时的副作用。©2023.作者。

APOBEC mutational signatures SBS2 and SBS13 are common in many human cancer types. However, there is an incomplete understanding of its stimulus, when it occurs in the progression from normal to cancer cell and the APOBEC enzymes responsible. Here we whole-genome sequenced 342 microdissected normal epithelial crypts from the small intestines of 39 individuals and found that SBS2/SBS13 mutations were present in 17% of crypts, more frequent than most other normal tissues. Crypts with SBS2/SBS13 often had immediate crypt neighbors without SBS2/SBS13, suggesting that the underlying cause of SBS2/SBS13 is cell-intrinsic. APOBEC mutagenesis occurred in an episodic manner throughout the human lifespan, including in young children. APOBEC1 mRNA levels were very high in the small intestine epithelium, but low in the large intestine epithelium and other tissues. The results suggest that the high levels of SBS2/SBS13 in the small intestine are collateral damage from APOBEC1 fulfilling its physiological function of editing APOB mRNA.© 2023. The Author(s).