Elucidating the Role of , , and Mutations and Microsatellite Instability in Colorectal Cancer via Next-Generation Sequencing.

METHODS

We retrospectively and cross-sectionally reviewed the cases of 648 patients with a 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).

RESULTS

A high mutation rate was found in the gene (52.4%). mutations were less frequent (8.9%), whereas mutations were observed in 20.8% of cases. This allowed us to identify a patient subgroup with MSI, representing 12.1% of cases. Among the 42 patients analyzed for , , , and MSI mutations, a significant association was observed between mutations and microsatellite stability, while no association was found between mutations and MSI. mutations showed a statistically significant association with MSI ( < 0.05), with the most common mutation being c.1799T > A, . The objective of this study is to demonstrate that the NGS-based method for evaluating MSI is rigorously valid compared to the results obtained using IHC and PCR.

CONCLUSIONS

Comprehensive NGS profiling from the start improves diagnostic efficiency by saving time, tissue, and costs compared to gene-by-gene analysis. It also enables better molecular characterization and facilitates tailored therapeutic strategies, particularly in identifying candidates for targeted therapy and immunotherapy. This approach supports efficient tumor classification based on using , , , , and as key markers, along with MSI status. We recommend that, if initial NGS is not feasible, start with analysis, then test and MSI if no mutation is found.