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学科主题: 临床医学
题名:
Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing
作者: Yu, Chang1; Yu, Jun2,3; Yao, Xiaotian1; Wu, William K. K.2,3; Lu, Youyong4; Tang, Senwei1,2,3; Li, Xiangchun1; Bao, Li1; Li, Xiaoxing2,3; Hou, Yong1,5,6; Wu, Renhua1; Jian, Min1; Chen, Ruoyan1,7; Zhang, Fan1,8; Xu, Lixia2,3; Fan, Fan1; He, Jun1,2,3; Liang, Qiaoyi2,3; Wang, Hongyi9; Hu, Xueda1; He, Minghui1; Zhang, Xiang2,3; Zheng, Hancheng1; Li, Qibin1; Wu, Hanjie1; Chen, Yan1; Yang, Xu1; Zhu, Shida1; Xu, Xun1; Yang, Huanming1; Wang, Jian1; Zhang, Xiuqing1; Sung, Joseph J. Y.2,3; Li, Yingrui1; Wang, Jun1,10,11,12
关键词: single-cell sequencing ; colon cancer ; SLC12A5 ; biclonal ; oncogene
刊名: CELL RESEARCH
发表日期: 2014-06-01
DOI: 10.1038/cr.2014.43
卷: 24, 期:6, 页:701-712
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: COLORECTAL CANCERS ; HUMAN BREAST ; TUMOR ; EVOLUTION ; MUTATION ; EXPRESSION
英文摘要:

Single-cell sequencing is a powerful tool for delineating clonal relationship and identifying key driver genes for personalized cancer management. Here we performed single-cell sequencing analysis of a case of colon cancer. Population genetics analyses identified two independent clones in tumor cell population. The major tumor clone harbored APC and TP53 mutations as early oncogenic events, whereas the minor clone contained preponderant CDC27 and PABPC1 mutations. The absence of APC and TP53 mutations in the minor clone supports that these two clones were derived from two cellular origins. Examination of somatic mutation allele frequency spectra of additional 21 whole-tissue exome-sequenced cases revealed the heterogeneity of clonal origins in colon cancer. Next, we identified a mutated gene SLC12A5 that showed a high frequency of mutation at the single-cell level but exhibited low prevalence at the population level. Functional characterization of mutant SLC12A5 revealed its potential oncogenic effect in colon cancer. Our study provides the first exome-wide evidence at single-cell level supporting that colon cancer could be of a biclonal origin, and suggests that low-prevalence mutations in a cohort may also play important protumorigenic roles at the individual level.

语种: 英语
所属项目编号: 2011CB809202 ; 2011CB809203 ; 2009AA022707 ; T12-403-11 ; ZYC201005250020A ; CXB200903110066A ; CXB201108250096A
项目资助者: National Basic Research Program of China (973 program) ; Hi-Tech Research and Development Program of China (863 program) ; Theme-based Research Scheme of the Hong Kong Research Grants Council ; Shenzhen Municipal Government of China ; Key Laboratory project Supported by Shenzhen City ; Shenzhen Key Laboratory of Gene Bank for National Life Science ; Innovative Research Team Project of GuangDong ; GuangDong Enterprise Key Laboratory of Human Disease Genomics ; Intramural Research Program of the National Institutes of Health ; National Cancer Institute ; Center for Cancer Research ; Cancer Genome Project, Scheme B CUHK ; Danish Natural Science Research Council for the Ole Romer grant ; Shenzhen Municipal Government and the Local Government of Yantian District of Shenzhen
WOS记录号: WOS:000337682900009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57712
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China
2.Chinese Univ Hong Kong, Inst Digest Dis, Hong Kong, Hong Kong, Peoples R China
3.Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Dept Med & Therapeut, State Key Lab Digest Dis, Hong Kong, Hong Kong, Peoples R China
4.Peking Univ, Beijing Canc Hosp Inst, Sch Oncol,Minist Educ, Lab Mol Oncol,Key Lab Carcinogenesis & Translat R, Beijing 100871, Peoples R China
5.Southeast Univ, Sch Biol Sci & Med Engn, Nanjing, Jiangsu, Peoples R China
6.Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Jiangsu, Peoples R China
7.Univ Hong Kong, Dept Peadiatr & Adolescent Med, Hong Kong, Hong Kong, Peoples R China
8.Univ Michigan, Sch Med, Dept Computat Med & Bioinformat, Ann Arbor, MI USA
9.Peking Univ, Beijing Canc Hosp Inst, Sch Oncol, Dept Surg, Beijing 100142, Peoples R China
10.Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark
11.King Abdulaziz Univ, Princess Jawhara Ctr Excellence Res Hereditary Di, Jeddah 21589, Saudi Arabia
12.Macau Univ Sci & Technol, Taipa 999078, Macau, Peoples R China

Recommended Citation:
Yu, Chang,Yu, Jun,Yao, Xiaotian,et al. Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing[J]. CELL RESEARCH,2014,24(6):701-712.
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