Colorectal Cancer Clues Provided by Polyp Profiles

They used a combination of whole-genome sequencing, RNA sequencing, and reduced-representation bisulfite sequencing (RRBS) to profile cancer-adjacent or cancer-free colorectal adenomatous polyp samples from dozens of individuals with or without colorectal cancer.

The team used HiSeq X instruments and collaborators at the Broad Institute did whole-genome sequencing on all of the available polyp samples, generating 30-fold average genome coverage of these samples. They also performed RNA-seq and RRBS paired-end sequencing on 69 and 76 samples, respectively, with Illumina HiSeq 2000 and/or 2500 instruments. The team noted that that the cancer-adjacent polyps (CAP) tissues taken from CRC-neighboring sites from 16 CAP cases included tissues from the residual polyp of origin and contiguous cancer. On the other hand, the cancer-free polyps (CFPs) came from 15 individuals with lesions that had not progressed to cancer.

The investigators reported that along with a significant uptick in somatic mutations, CAPs showed altered expression of genes such as GREM1 or IGF2 and a sharp rise in methylation in many portions of the genome, relative to the CFP. While genes such as APC, KRAS, and BRAF were significantly mutated in cancer-free and cancer-adjacent polyps, other genes appeared to have CAP-specific mutations; a set that included TP53, SMAD2/4, and PIK3CA. The integrative analyses, brought together molecular data from all three of the approaches used to characterize the samples, highlighted 124 genes with CAP-related alterations revealed by two or more molecular alteration types. The study was published on February 16, 2018, in the journal Scientific Reports.

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