Molecular Characterization of Sporadic Colorectal Cancer: Association Between KRAS, NRAS, and BRAF Mutations and Microsatellite Instability via Next-Generation Sequencing

We retrospectively and cross-sectionally reviewed 648 cases with histological diagnosis of colon adenocarcinoma. Of these, 166 had partial molecular studies, and 42 cases were selected based on the availability of the genetic markers targeted in this study. We analyzed the frequency of mutations in these genes, as well as their correlation with microsatellite instability (MSI). A high mutation rate was found in KRAS (52.4%). NRAS mutations were less frequent (8.9%), whereas BRAF mutations were observed in 20.8% of cases. This finding identifies a patient subgroup with MSI, present in 12.1% of cases. Among the 42 patients analyzed for KRAS, NRAS, BRAF, and MSI, a significant association was observed between KRAS mutations and microsatellite stability, while no association was found between NRAS mutations and MSI.As expected, BRAF mutations showed a statistically significant association with MSI (p < 0.05), with the most common mutation being c.1799T>A, p.(Val600Glu). Comprehensive NGS profiling from the start improves diagnostic efficiency by saving time, tissue, and costs compared to gene-by-gene analysis. At the same time, it enables better molecular characterization and facilitates tailored therapeutic strategies, particularly in identifying candidates for targeted therapy and immunotherapy. This approach supports an efficient classification of tumors based on KRAS and BRAF as key markers, along with MSI status. If initial NGS is not feasible, start with KRAS analysis, then test BRAF and MSI if no mutation is found.