Abstract：
Polyketide synthase (pks) island harboring Escherichia coli are, under the right circumstances, able to produce the genotoxin colibactin. Colibactin is a risk factor for the development of colorectal cancer and associated with mutational signatures SBS88 and ID18. This study explores colibactin-associated mutational signatures in biallelic NTHL1 and MUTYH patients. Targeted Next Generation Sequencing (NGS) was performed on colorectal adenomas and carcinomas of one biallelic NTHL and 12 biallelic MUTYH patients. Additional fecal metagenomics and genome sequencing followed by mutational signature analysis was conducted for the NTHL1 patient. Targeted NGS of the NTHL1 patient showed somatic APC variants fitting SBS88 which was confirmed using WGS. Furthermore, fecal metagenomics revealed pks genes. Also, in 1 out of 11 MUTYH patient a somatic variant was detected fitting SBS88. This report shows that colibactin may influence development of colorectal neoplasms in predisposed patients.
摘要：
聚酮化合物合成酶（PKS）岛有大肠杆菌，在适当的情况下,能够产生基因毒素大肠杆菌素。Colibactin是结直肠癌发展的危险因素，与SBS88和ID18突变相关。这项研究探讨了双等位基因NTHL1和MUTYH患者中与colibactin相关的突变特征。对1例双等位基因NTHL和12例双等位基因MUTYH患者的结直肠腺瘤和癌进行靶向下一代测序(NGS)。对NTHL1患者进行额外的粪便宏基因组学和基因组测序，然后进行突变特征分析。NTHL1患者的靶向NGS显示出符合SBS88的体细胞APC变体，这是用WGS证实的。此外，粪便宏基因组学揭示了pks基因。此外，在11例MUTYH患者中，有1例检测到符合SBS88的体细胞变异。该报告表明，大肠杆菌素可能会影响易感患者结直肠肿瘤的发展。
