Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing

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 and Wang, Jun (2014) Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing. Cell Research, 24 701-712. doi:10.1038/cr.2014.43


Author 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
Title Discovery of biclonal origin and a novel oncogene SLC12A5 in colon cancer by single-cell sequencing
Journal name Cell Research   Check publisher's open access policy
ISSN 1748-7838
1001-0602
Publication date 2014-04-04
Year available 2015
Sub-type Article (original research)
DOI 10.1038/cr.2014.43
Open Access Status Not Open Access
Volume 24
Start page 701
End page 712
Total pages 12
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted 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.
Keyword Single-cell sequencing
Colon cancer
SLC12A5
Biclonal
Oncogene
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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