Abstract 2566: Molecular characteristic profile in early colorectal cancer with V600E and non-V600E BRAF mutations
Authors: An Zhang Quan 
Published: March 2024

Abstract
Background: The BRAF V600E mutation in colorectal cancer (CRC) is a significant indicator of poor prognosis, especially in tumors exhibiting microsatellite instability (MSI). It is more common on the right side of the colon but can occur anywhere within the colon. Although other BRAF mutations existed, current research primarily focused on BRAF V600E. Most clinical data sets were centered on advanced colorectal cancer. There was limited understanding of the molecular characteristics of early-stage colorectal cancer patients with BRAF mutations, which impacted postoperative prognosis management, including refining adjuvant therapy regimens. Therefore, we analyzed the molecular characteristics of early-stage CRC surgical patients.
Methods: Tumor tissue from 767 early-stage CRC patients diagnosed between 2021 to 2022 in China were analyzed using NGS (panel on 733 gene) to validate the mutation characteristics. Tumor specimens were tested for the BRAF mutation and MSI status.
Result: Among 767 early CRC cases tested, BRAF mutations accounted for 6.52% (50/767), with 62% (31/50) being BRAF V600E, followed by 14% (7/50) for BRAF D594G. Notably, there were two cases of fusion variations, TRIM24-BRAF, and one case of BRAF copy gain. Among the BRAF mutation population, 11 cases were MSI-H, with 8 of them being BRAF V600E/MSI-H. Only one MSH-H patient had a germline mutation in the MLH1 gene, with a concurrent mutation in BRAF K601T.Interestingly, when comparing the mutation profiles of the BRAF V600E population with those of the non-V600E BRAF mutation population, we found distinct co-mutated genes despite both being BRAF mutations. In the BRAF V600E group, the top three frequently mutated genes were TP53 (52%), RNF43 (32%), and SMAD4 (32%). Additionally, the BRAF V600E/MSI-H subgroup presented a distinct mutation profile, with minimal occurrences of TP53 and SMAD4 mutations. In the non-V600E BRAF mutation group, the top three frequently mutated genes were TP53 (84%), APC (63%), and KRAS (32%).
Conclusions: In examining the mutation profile characteristics of early colorectal cancer with BRAF mutations, the proportion of BRAF V600E/MSI-H appeared to have been lower than that reported in advanced cases. Furthermore, in terms of the frequency of co-mutated genes, it seemed that BRAF V600E had exhibited a higher malignant driving mutation effect as a single gene, while non-V600E mutations had required more cooperative tumor suppressor genes or oncogenes. Analyzing the molecular characteristics of early colorectal cancer patients with V600E and non-V600E BRAF mutations could help improve postoperative management and further our understanding of tumor progression.
Citation Format: Zhang Quan An. Molecular characteristic profile in early colorectal cancer with V600E and non-V600E BRAF mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2566.