IDDF2018-ABS-0096 Major genetic alterations in sporadic colorectal cancer in the chinese population

Abstract

Background Sporadic colorectal cancer accounts for 80% of all colorectal cancer. The 2 major mechanisms of genetic alteration are chromosomal instability (CIN) and microsatellite instability (MSI). The prevalence of KRAS, NRAS, BRAF and CTNNB1 mutations in western population was 42.4%, 5.1%, 15.2% and 1.1%. BRAF mutations in Chinese population were much lower (3.1%). RNF43 mutation was recently reported with a high prevalence of 18%. It was found mutually exclusive with APC inactivation and was associated with MSI-H tumours. In this study, the prevalence of APC, KRAS, NRAS, BRAF, CTNNB1 and RNF43 mutations in Chinese sporadic colorectal cancer patients was confirmed by next generation sequencing (NGS). The association of RNF43 mutation with APC, BRAF mutations and MSI status of tumours, was analysed. Clinical-pathological correlation was evaluated. Methods NGS was used to investigate the prevalence of major mutations in 55 subject samples. Data analysis was done by Statistical Package of the Social Sciences (SPSS) statistics. Clinical-pathological correlation was analysed by Cox regression and Kaplan-Meier estimate. Results The frequency of APC, KRAS, NRAS, BRAF, CTNNB1 and RNF43 mutations were 76.4%, 61.8%, 9.1%, 3.6%, 1.8% and 9.1%. The most common RNF43 mutation was p.Gly659fs. RNF43 mutation was associated with MSI-H status (p Conclusions The frequency of major mutations in Chinese population was stable. RNF43 mutation is likely anti-EGFR therapy resistant and is an alternative to targeted therapy. The current clinical classification of colorectal cancer and blood tests for disease monitoring were the most effective way to predict clinical prognosis. More research of larger sample size on the pathogenicity of RNF43 mutation and clinical correlation of major mutations is required.