Colorectal cancer tumor phenotypes associated with KRAS, NRAS, and BRAF hot-spot mutations.

Background: Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) nucleotide variants may generate quantitatively or qualitatively various protein activities, which may be reflected in their differential association with tumor characteristics.

Aim: To examine the association between these mutations and colorectal cancer (CRC) progression stages.

Methods: A retrospective analysis was conducted on 799 patients with CRC, whose tumor samples were examined for mutations in the hot-spots of the KRAS, NRAS, and BRAF genes at the University of Texas Medical Branch, spanning from January 2016 to July 2023. Statistical analyses were performed to assess the association of specific nucleotide changes with tumor, nodes, and metastasis stages.

Results: KRAS mutations were found in 39.5% of cases, NRAS mutations in 4.4%, and BRAF mutations in 6.0%. The KRAS p.Gly12Val and p.Gly13Asp mutations were positively associated with pathological stage 4 tumors. Additionally, the KRAS p.Gly12Asp and p.Gly12Val mutations were linked to an increased risk of distant metastasis. Meanwhile, the BRAF Val600Glu mutation was associated with a higher likelihood of lymph node involvement.

Conclusion: Our findings support the potential prognostic utility of specific KRAS (p.Gly12Val, p.Gly12Asp, and p.Gly13Asp) and BRAF p.Val600Glu mutations in CRC. These results are preliminary and require validation through larger, multi-center studies before they can be considered reliable in clinical practice.