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DOI | 10.1038/s41586-020-2080-8 |
Mutational signature in colorectal cancer caused by genotoxic pks(+)E. coli | |
Lin, Xi1,2,3,4; Li, Mingyue2,3,4; Wang, Niandong1,2,3,4; Wu, Yiran1; Luo, Zhipu5; Guo, Shimeng6; Han, Gye-Won7; Li, Shaobai8,9; Yue, Yang1; Wei, Xiaohu2,3,4; Xie, Xin2; Chen, Yong2,3,4; Zhao, Suwen1,2; Wu, Jian8,9,10; Lei, Ming8,9,11; Xu, Fei1,2,12 | |
2020-02-19 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2020 |
卷号 | 580期号:7802页码:269-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Netherlands; England; USA; France |
英文关键词 | Various species of the intestinal microbiota have been associated with the development of colorectal cancer(1,2), but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin(3). This compound is believed to alkylate DNA on adenine residues(4,5) and induces double-strand breaks in cultured cells(3). Here we expose human intestinal organoids to genotoxic pks(+)E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in colorectal cancer. Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island. Organoids derived from human intestinal cells that are co-cultured with bacteria carrying the genotoxic pks(+) island develop a distinct mutational signature associated with colorectal cancer. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000521704600001 |
WOS关键词 | ADULT STEM-CELLS ; ACCUMULATION ; ORGANOIDS ; EXPANSION ; INSIGHTS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/281505 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.ShanghaiTech Univ, iHuman Inst, Shanghai, Peoples R China; 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China; 4.Univ Chinese Acad Sci, Beijing, Peoples R China; 5.Soochow Univ, Sch Biol & Basic Med Sci, Inst Mol Enzymol, Suzhou, Peoples R China; 6.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai, Peoples R China; 7.Univ Southern Calif, Bridge Inst, Dept Biol Sci, Los Angeles, CA USA; 8.Shanghai Jiao Tong Univ, Peoples Hosp 9, Sch Med, Shanghai, Peoples R China; 9.Shanghai Inst Precis Med, Shanghai, Peoples R China; 10.Shanghai Key Lab Translat Med Ear & Nose Dis, Shanghai, Peoples R China; 11.Shanghai Jiao Tong Univ, Sch Med, Chinese Minist Educ, Key Lab Cell Differentiat & Apoptosis, Shanghai, Peoples R China; 12.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai, Peoples R China |
推荐引用方式 GB/T 7714 | Lin, Xi,Li, Mingyue,Wang, Niandong,et al. Mutational signature in colorectal cancer caused by genotoxic pks(+)E. coli[J]. NATURE,2020,580(7802):269-+. |
APA | Lin, Xi.,Li, Mingyue.,Wang, Niandong.,Wu, Yiran.,Luo, Zhipu.,...&Xu, Fei.(2020).Mutational signature in colorectal cancer caused by genotoxic pks(+)E. coli.NATURE,580(7802),269-+. |
MLA | Lin, Xi,et al."Mutational signature in colorectal cancer caused by genotoxic pks(+)E. coli".NATURE 580.7802(2020):269-+. |
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