Relationship between CpG island methylation phenotype, microsatellite instability phenotype and mutation of KRAS, NRAS, and BRAF genes in colorectal cancer

Objective: CpG island methylation phenotype (CIMP) and microsatellite instability (MSI) are two different molecular mechanisms in colorectal cancer (CRC). Proto-oncogene KRAS, mutations in NRAS and BRAF play an important role in the formation of colorectal cancer. The correlation between the molecular typing of CIMP and MSI and the genes of KRAS, NRAS and BRAF was explored in this study. Methods: A total of 110 paraffin-embedded specimens of colorectal cancer were collected from the Chinese People's Liberation Army Rocket Army Special Medical Center during the period from May 2017 to September 2018. CIMP were detected by DNA methylation quantitative PCR (Methylight). Mutations in KRAS, NRAS, and BRAF genes were detected by realtime fluorescence quantitative PCR (qPCR); MSI typing was detected by sequencing. Results: Of the 110 colorectal cancer samples, 11 cases (10%) were CIMP-H, 92 cases (83.64%) were CIMP-L, and 7 cases (6.36%) were CIMP-0.10 cases (9.09%) were MSI-H, and 100 cases (90.91%) were MSS and MSI-L. The mutation rates of KRAS, NRAS and BRAF genes were 50% (55 cases), 6.36% (7 cases) and 5.45% (6 cases), respectively. There was no significant correlation between CIMP group and MSI group (P > 0.05). Also, no significant differences were found in the mutations between the three subtypes of the CIMP group and the KRAS, NRAS genes (P > 0.05), while there was a statistically significant difference among the three subtypes of the BR and the BRAF gene mutations (P < 0.0001). There were no obvious differences between the three states of microsatellites and the mutations of KRAS and NRAS genes (P > 0.05), and the differences between them and BRAF gene mutations were statistically significant (P < 0.01). Conclusions: The BRAF gene mutation is closely related to the two types of CIMP and MSI, which may be an important part of the above two molecular mechanisms, and provide a reference for the treatment of the patients with CIMP-H and MSI-H.