Somatic mutations in colorectal cancer are associated with the epigenetic modifications

Colorectal Cancer

J Cell Mol Med. 2020 Aug 31. doi: 10.1111/jcmm.15799. Online ahead of print.


Colorectal cancer (CRC) mostly arises from progressive accumulation of somatic mutations within cells. Most commonly mutated genes like TP53, APC and KRAS can promote survival and proliferation of cancer cells. Although the molecular alterations and landscape of some specific mutations in CRC are well known, the presence of a somatic mutation signature related to genomic regions and epigenetic markers remain unclear. To find the signatures from a random distribution of somatic mutations in CRCs,

we carried out enrichment analysis in different genomic regions and identified peaks of epigenetic markers. We validated that the mutation frequency in miRNA is dramatically higher than in flanking genomic regions. Moreover, we observed that somatic mutations in CRC and colon cancer cell lines are significantly enriched in CTCF binding sites. We also found these mutations are enriched for H3K27me3 in both normal sigmoid colon and colon cancer cell lines. Taken together, our findings suggest that there are some common somatic mutations signatures which provide new directions to study CRC.