Abstract 5536: Landscape and analysis of ERBB2 amplification and short variant mutations in large-scale Chinese patients with colorectal cancer

Abstract

Abstract Background: Human epidermal growth factor receptor 2 (ERBB2) amplification is a rapidly emerging therapeutic target in CRC, in spite of a relatively low incidence. While ERBB2 amplification has been considered as a critical biomarker to predict the efficacy and safety of anti-ERBB2 therapy of CRC, its point mutation status is largely ambiguous.Methods: Blood or tissues samples from 2454 Chinese patients with CRC were collected, and the genomic landscape, clinical characteristics and genetic features of ERBB2 in these samples were retrospectively investigated using next-generation sequencing (NGS) analysis. Results: Of the 2454 colorectal cancer patients, 3.46% (85) carried ERBB2 amplification, 2.24% (55) carried ERBB2 mutation, and some patients harbored both ERBB2 amplification and point mutation at the same time. Microsatellite instability high (MSI-H) was found in approximately 32.7% (18/55) of patients with ERBB2-mutated CRC, but almost negative in ERBB2-amplified CRC. The median fold change of ERBB2 amplification was 30 (Range 4 to 245). Among the 16 mutation sites detected from 55 patients with ERBB2 point mutations, p.R678Q was the most common mutation site (28%), followed by p.V842I (24%) and p.S310F/Y (12%), which appeared to be slightly different from previous reports. ERBB2 mutation was more frequently found in CRC patients aged < 50 years. 50.9% of CRC patients with wild-type ERBB2 carried KRAS mutation, which was significantly higher than those with mutated ERBB2 (25.6%). A higher incidence of BRAF mutation was observed in patients with mutated-ERBB2 (8.5% vs. 2.3%). In addition, CRC patients with ERBB2 CNV showed a higher prevalence of TP53 mutation comparing with those with ERBB2 SNV (92.3% vs. 58.3%), while KRAS mutation exhibited a contrary trend (14.1% vs. 45.8%)Conclusions: The overall variation rate of ERBB2 is 5.4% in Chinese patients with CRC, which is accompanied by significantly different molecular pathological characteristics compared to patients with wild-type ERBB2, and different mutation types (CNV or SNV) display different molecular pathological characteristics. Citation Format: Zhiqin Chen, Shijun Yu, Yin Wu, Bei Zhang, Ding Zhang, Yong Gao, Ming Quan. Landscape and analysis of ERBB2 amplification and short variant mutations in large-scale Chinese patients with colorectal cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5536.