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


引用次數
替代計量分析
.

其它資訊
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.
著者Yu C, Yu J, Yao XT, Wu WKK, Lu YY, Tang SW, Li XC, Bao L, Li XX, Hou Y, Wu RH, Jian M, Chen RY, Zhang F, Xu LX, Fan F, He J, Liang QY, Wang HY, Hu XD, He MH, Zhang X, Zheng HC, Li QB, Wu HJ, Chen Y, Yang X, Zhu SD, Xu X, Yang HM, Wang J, Zhang XQ, Sung JJY, Li YR, Wang J
期刊名稱Cell Research
出版年份2014
月份6
日期1
卷號24
期次6
出版社Nature Publishing Group: Open Access Hybrid Model Option B
頁次701 - 712
國際標準期刊號1001-0602
電子國際標準期刊號1748-7838
語言英式英語
關鍵詞biclonal; colon cancer; oncogene; single-cell sequencing; SLC12A5
Web of Science 學科類別Cell Biology

上次更新時間 2020-30-11 於 00:35