Clinical Characterization of Targetable Mutations (BRAF V600E and KRAS G12C) in Advanced Colorectal Cancer-A Nation-Wide Study

by Selleckchem | Aug 30 2023

BRAF V600E and KRAS mutations that occur in colorectal cancer (CRC) define a subpopulation of patients with an inferior prognosis. Recently, the first BRAF V600E-targeting therapy has been approved and novel agents targeting KRAS G12C are being evaluated in CRC. A better understanding of the clinical characteristics of the populations defined by those mutations is needed. We created a retrospective database that collects clinical characteristics of patients with metastatic CRC evaluated for RAS and BRAF mutations in a single laboratory. A total of 7604 patients tested between October 2017 and December 2019 were included in the analysis. The prevalence of BRAF V600E was 6.77%. Female sex, primary in the right colon, high-grade, mucinous, signet cell, partially neuroendocrine histology, perineural and vascular invasion, and surgical tissue sample were factors associated with increased mutation rates. The prevalence of KRAS G12C was 3.11%. Cancer of primary origin in the left colon and in samples from brain metastases were associated with increased mutation rates. The high prevalence of the BRAF V600E mutation in cancers with a neuroendocrine component identifies a potential candidate population for BRAF inhibition. The association of KRAS G12C with the left part of the intestine and brain metastases of CRC are new findings and require further investigation.

Comments:

The information you provided describes a retrospective database analysis that aimed to understand the clinical characteristics of patients with metastatic colorectal cancer (CRC) and specific mutations, namely BRAF V600E and KRAS G12C. Here are the key findings from the analysis:

1. Prevalence of BRAF V600E: Among the 7,604 patients tested between October 2017 and December 2019, the prevalence of the BRAF V600E mutation was 6.77%. This mutation is associated with an inferior prognosis in CRC.

2. Factors associated with BRAF V600E mutation: The following clinical characteristics were associated with an increased mutation rate of BRAF V600E:
   - Female sex
   - Primary tumor location in the right colon
   - High-grade histology
   - Mucinous, signet cell, and partially neuroendocrine histology
   - Presence of perineural and vascular invasion
   - Surgical tissue sample

3. Prevalence of KRAS G12C: The analysis found that the prevalence of the KRAS G12C mutation was 3.11% among the tested patients.

4. Factors associated with KRAS G12C mutation: The following clinical characteristics were associated with an increased mutation rate of KRAS G12C:
- Cancer originating in the left colon
- Samples from brain metastases

5. Potential implications and future investigations:
- The high prevalence of BRAF V600E mutation in cancers with a neuroendocrine component suggests that patients with this mutation may benefit from BRAF inhibition therapy.
- The association of KRAS G12C mutation with the left part of the intestine and brain metastases in CRC is a novel finding and warrants further investigation.

Overall, this retrospective analysis provides important insights into the clinical characteristics of patients with metastatic CRC and specific mutations, highlighting potential therapeutic opportunities and the need for further research.