Multi-region and single-cell sequencing reveal variable genomic heterogeneity in rectal cancer

BMC Cancer

Zhe Su¹  Mingshan Liu¹  Fan Bai¹  Yang Liu¹  Jiabo Di²  Beihai Jiang²  Zaozao Wang²  Xiangqian Su²  Meng Zhuang²  Hong Yang² 

[1] Biodynamics Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University;Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute;

关键词: Rectal cancer;    Single-cell whole-genome sequencing;    Multi-region whole-exome sequencing;    Somatic copy number alterations;    Intratumor heterogeneity;   

DOI  :  10.1186/s12885-017-3777-4

来源: DOAJ

【 摘 要 】

Abstract Background Colorectal cancer is a heterogeneous group of malignancies with complex molecular subtypes. While colon cancer has been widely investigated, studies on rectal cancer are very limited. Here, we performed multi-region whole-exome sequencing and single-cell whole-genome sequencing to examine the genomic intratumor heterogeneity (ITH) of rectal tumors. Methods We sequenced nine tumor regions and 88 single cells from two rectal cancer patients with tumors of the same molecular classification and characterized their mutation profiles and somatic copy number alterations (SCNAs) at the multi-region and the single-cell levels. Results A variable extent of genomic heterogeneity was observed between the two patients, and the degree of ITH increased when analyzed on the single-cell level. We found that major SCNAs were early events in cancer development and inherited steadily. Single-cell sequencing revealed mutations and SCNAs which were hidden in bulk sequencing. In summary, we studied the ITH of rectal cancer at regional and single-cell resolution and demonstrated that variable heterogeneity existed in two patients. The mutational scenarios and SCNA profiles of two patients with treatment naïve from the same molecular subtype are quite different. Conclusions Our results suggest each tumor possesses its own architecture, which may result in different diagnosis, prognosis, and drug responses. Remarkable ITH exists in the two patients we have studied, providing a preliminary impression of ITH in rectal cancer.

【 授权许可】

Unknown