Integrated molecular profiling of , mutations, and mismatch repair status in advanced colorectal carcinoma: insights from gender and tumor laterality.

BACKGROUND

Colorectal carcinoma (CRC) is one of the most frequently diagnosed forms of cancer worldwide. The (, ) and genes encode proteins that are important therapeutic targets for the treatment of CRC and, together with the mismatch repair (MMR) system, are closely related to patient prognosis and survival in advanced CRC. Here we evaluate the mutational profile and the frequency of mutations in the , and genes, along with the expression of MMR in advanced CRC, at a tertiary hospital in southern Brazil.

METHODS

A cross-sectional retrospective study was carried out, where molecular analysis of mutations in the , and genes was carried out, as well as immunohistochemistry for MMR proteins.

RESULTS

Next-generation sequencing (NGS) analysis of 310 tumors revealed that 202 patients (65.2%) had mutations. The gene (53.2%) was the most frequently mutated in our sample, with G12D being the most frequent, representing 30.5% of the mutations in this gene. The most frequent mutation found in was V600E (n=25; 89.3%) and differed significantly in women and in the right colon in patients with MMR deficiency. Among the 283 patients tested for MMR, the rate of loss of expression was 8.8% (25/283).

CONCLUSIONS

Deficiency in the MMR system is associated with the presence of the V600E mutation, tumors located in the right colon, and the female sex. In our case series, more than 60% of patients had at least one mutation in , , or . The presence of mutations in these genes is closely related to CRC prognosis and helps define the best therapeutic approach in patients with metastatic CRC.