Title | Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing |
Authors | Yu, Chang Yu, Jun Yao, Xiaotian Wu, William K. K. Lu, Youyong Tang, Senwei Li, Xiangchun Bao, Li Li, Xiaoxing Hou, Yong Wu, Renhua Jian, Min Chen, Ruoyan Zhang, Fan Xu, Lixia Fan, Fan He, Jun Liang, Qiaoyi Wang, Hongyi Hu, Xueda He, Minghui Zhang, Xiang Zheng, Hancheng Li, Qibin Wu, Hanjie Chen, Yan Yang, Xu Zhu, Shida Xu, Xun Yang, Huanming Wang, Jian Zhang, Xiuqing Sung, Joseph J. Y. Li, Yingrui Wang, Jun |
Affiliation | BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China. Chinese Univ Hong Kong, Inst Digest Dis, Hong Kong, Hong Kong, Peoples R China. 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. Peking Univ, Beijing Canc Hosp Inst, Sch Oncol,Minist Educ, Lab Mol Oncol,Key Lab Carcinogenesis & Translat R, Beijing 100871, Peoples R China. Southeast Univ, Sch Biol Sci & Med Engn, Nanjing, Jiangsu, Peoples R China. Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Jiangsu, Peoples R China. Univ Hong Kong, Dept Peadiatr & Adolescent Med, Hong Kong, Hong Kong, Peoples R China. Univ Michigan, Sch Med, Dept Computat Med & Bioinformat, Ann Arbor, MI USA. Peking Univ, Beijing Canc Hosp Inst, Sch Oncol, Dept Surg, Beijing 100142, Peoples R China. Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark. King Abdulaziz Univ, Princess Jawhara Ctr Excellence Res Hereditary Di, Jeddah 21589, Saudi Arabia. Macau Univ Sci & Technol, Taipa 999078, Macau, Peoples R China. |
Keywords | single-cell sequencing colon cancer SLC12A5 biclonal oncogene COLORECTAL CANCERS HUMAN BREAST TUMOR EVOLUTION MUTATION EXPRESSION |
Issue Date | 2014 |
Publisher | 细胞研究英文版 |
Citation | CELL RESEARCH.2014,24,(6),701-712. |
Abstract | 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. |
URI | http://hdl.handle.net/20.500.11897/189555 |
ISSN | 1001-0602 |
DOI | 10.1038/cr.2014.43 |
Indexed | SCI(E) PubMed 中国科技核心期刊(ISTIC) 中国科学引文数据库(CSCD) |
Appears in Collections: | 北京肿瘤医院 |