Mutation Analysis Of Kras And Braf Hotspots In Moroccan Patients With Colorectal Cancer

Background: Oncogenic activation of the RAS/RAF signaling pathway induces resistance to anti-epidermal growth factor receptor targeted therapies in patients with colorectal cancer. We investigated the occurrence of BRAF exon 15 and KRAS codons 12 and 13 mutations in patients with colorectal cancer. Patients and Methods: Forty-seven samples from patients with metastasic colorectal adenocarcinomas were studied for BRAF exon 15 and KRAS codons 12 and 13 mutations. From formalin-fixed paraffin-embedded tissue specimens, macrodissection was used to remove specifically the tumor tissue. After DNA extraction, conventional PCR was performed and the DNA was analyzed by direct sequencing. Results: KRAS codon 12 or 13 mutations were present in 51% of patients. Gly12Val mutation was present in 21% of all patients, Gly12Asp in 15%, Gly13Asp in 6%, Gly12Arg in 4%, Gly12Cys in 2% and Gly12Ala in 2%. No BRAF mutation was highlighted. Conclusion: Our data suggest that KRAS mutations are more frequently than BRAF mutations in Moroccan patients with colorectal carcinomas. To our knowledge, we are the first to report such a high proportion (more than 50%) of potentially non responsive patients for the anti-EGFR treatment in Morocco. These results show that, without doubt, the method we used was accurate, cost-effective and time-efficient.