生物
突变
大肠杆菌
遗传学
基因组
结直肠癌
全基因组测序
癌症
基因
作者
Axel Rosendahl Huber,Cayetano Pleguezuelos-Manzano,Jens Puschhof,Joske Ubels,Charelle Boot,Aurelia Saftien,Mark Verheul,Laurianne Trabut,Niels M. Groenen,Markus Van Roosmalen,Karen Ouyang,Henry M. Wood,Philip Quirke,Gerrit A. Meijer,Edwin Cuppen,Hans Clevers,Ruben van Boxtel
出处
期刊:Cancer Cell
[Elsevier]
日期:2024-03-01
卷期号:42 (3): 487-496.e6
标识
DOI:10.1016/j.ccell.2024.02.009
摘要
Summary
Co-culture of intestinal organoids with a colibactin-producing pks+ E. coli strain (EcC) revealed mutational signatures also found in colorectal cancer (CRC). E. coli Nissle 1917 (EcN) remains a commonly used probiotic, despite harboring the pks operon and inducing double strand DNA breaks. We determine the mutagenicity of EcN and three CRC-derived pks+ E. coli strains with an analytical framework based on sequence characteristic of colibactin-induced mutations. All strains, including EcN, display varying levels of mutagenic activity. Furthermore, a machine learning approach attributing individual mutations to colibactin reveals that patients with colibactin-induced mutations are diagnosed at a younger age and that colibactin can induce a specific APC mutation. These approaches allow the sensitive detection of colibactin-induced mutations in ∼12% of CRC genomes and even in whole exome sequencing data, representing a crucial step toward pinpointing the mutagenic activity of distinct pks+ E. coli strains.
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