Mutation profiling of BRAF gene in Chinese patients with early or advanced colorectal cancer using comprehensive NGS panel.

Abstract

e15124 Background: It has been reported that BRAF gene mutation occurs in approximately 10% of metastatic colorectal cancer (mCRC), and is associated with resistance to EGFR inhibitors. Moreover, patients with non-V600E BRAF mutations with a better prognosis than patients with V600E BRAF mutations in advanced colorectal cancer. However, little is known about mutation profiling of BRAF in early stage colorectal cancer. Methods: We reviewed mutation profiling of 1429 colorectal cancer samples in our institute from 2016 to 2018. Tissue biopsy and/or ctDNA samples were analyzed using hybridization capture-based NGS ER-Seq method, which enables simultaneously assess single-nucleotide variants, insertions/deletions, rearrangements, and somatic copy-number alterations at least 59 genes (range 59-1021 genes). Results: A total of 1429 samples from 1120 patients with CRC, included 86 early stage (Ⅰ-Ⅱ ), 966 advanced stage (Ⅲ -Ⅳ), and 377 samples with unknown stage. We identified 109 samples from 94 patients with BRAF gene mutation in the cohort (109/1429=7.63%), of which V600E and non-V600E were 62(4.34%) and 47 (3.29%), respectively. Among the 109 samples, there were 15 of early stage, 84 of advanced stage and 10 of unknown stages. BRAF mutation were more common in early CRC samples (15/86=17.44%) than in advanced CRC samples (84/966=8.7%, p = 0.007). Furthermore, 10 of the 15 early CRC samples yet 32 of the 84 mCRC samples had non-V600E were detected (66.67% vs 38.1%, p=0.039). In contrast to V600E mutation, some of the non-V600E variants were variants of unknown clinical significance (VUS) in this study (see Table). Conclusions: BRAF mutation is more common in early stage CRC, the higher prevalence of non-V600E BRAF mutations in early CRC may account for the better prognosis of early stage CRC. non-V600E BRAF mutation subtype. [Table: see text]