Abstract 3621: Characterization of BRAF mutation in Chinese colorectal cancer patients using next generation sequencing

Abstract

Abstract Objective: BRAF alterations were characterized into three classes according to their dependency with upstream gene alterations in activating the MARK signaling pathway, giving clinical doctors clues of inhibitors selection for therapy. However, the characterization of BRAF mutation in Chinese colorectal cancer patients was unknown. Methods: Colorectum tissue samples were collected from 2155 patients and performed the next generation sequencing (NGS) using a validated commercial panel containing essential genes in RAS-RAF-MARK and PI3K-AKT-mTOR pathways. BRAF mutations were characterized into Class I (kinase-activated, codon 600), II (kinase-activated, non-codon 600) and III (kinase-impaired). Results: There were 9031 pathogenic and likely pathogenic somatic mutations were detected in 2137 out of 2155 samples, among which 149 (7.0%), 1048 (48.6%), 82 (3.8%), 2 (0.1%), 8 (0.4%), 362 (16.8%), 90 (4.2%) were found caring BRAF, KRAS, NRAS, HRAS, EGFR, PIK3CA and PTEN mutations, respectively. A total of 19 unique BRAF mutations were detected. The Class I (BRAFV600E), Class II and Class III accounted for 76.0%, 6.7% and 13.3% of all BRAF mutations. Higher incidence of co-occurrence of Class III mutations and RAS mutations were observed in our study, which might be due to their RAS-dependent way in activating downstream signaling pathway. Class III patients might be more sensitive to EGFR inhibitor and receive more benefits from survival than other classes. Conclusions: In our study, the mutation type, frequency, classification of BRAF mutations and co-occurrence with BRAF and other driver gene mutations were explored in a large cohort of Chinese colorectal cancer patients, which might help to suggest proper therapy methods. Citation Format: Hui Wang, Hao Wu, Yifan Zhou, Bei Zhang, Danpeng Sun, LIihua Jiang, Hui Chen, Yuezong Bai, Zhe Zhang. Characterization of BRAF mutation in Chinese colorectal cancer patients using next generation sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3621.