Abstract
BackgroundColorectal 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.MethodsWe 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.ResultsA 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.ConclusionsOur 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.
Highlights
Colorectal cancer is a heterogeneous group of malignancies with complex molecular subtypes
Multi-region whole-exome sequencing (WES) revealed variable genomic heterogeneity To depict the genomic heterogeneity of rectal cancer, multi-region WES was performed to determine the mutation distribution and somatic copy number alterations (SCNAs) profiles in the two rectal primary tumors
The two fresh primary rectal tumors were of the same molecular subtype [28], which was microsatellite stable, chromosomal instable, and/or mutant TP53 with wildtype KRAS and PIK3CA (Additional file 1: Table S1)
Summary
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. We performed multi-region whole-exome sequencing and single-cell whole-genome sequencing to examine the genomic intratumor heterogeneity (ITH) of rectal tumors. Colorectal cancer is highly heterogeneous, and its pathogenesis and molecular classification have been widely investigated [1, 2]. A notable feature of cancer, has recently been studied in breast cancer [4], esophageal cancer [5], renal cancer [6, 7] and lung cancer [8, 9] through multi-region sequencing of tumor masses. Tumor heterogeneity of colorectal cancer, especially rectal cancer, was less investigated.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
