Pharmaceutical Research & Developmen   (Track)

BRAF AND KRAS MUTATIONS IN ALGERIAN PATIENTS WITH METASTATIC COLORECTAL CANCER

K. Berkane, H. Benchaa and K. Bouzid

Molecular Oncology Laboratory, Medical Oncology Department, Pierre & Marie Curie Center, Algiers, Algeria

Abstract

Objectives: Colorectal cancer (CRC) is the second most common cancer in Algeria. This study is one of the first to analyze molecular profile in Algerian patients with CRC which can predict prognosis and contribute to decisions on treatment strategies.

Material and Methods: We examined the clinico-pathological features and molecular profile of KRAS exon 2, BRAF exon 15 and MSI from Algerian patients with advanced or m CRC. DNA in paraffin-embedded tissue specimens was analyzed by direct sequencing of amplified PCR products. Microsatellite instability was determined using five mononucleotide markers (BAT25, BAT26, NR21, NR22, NR24).

Results: BRAF and KRAS mutations were detected in 4.9% and 31.3% of the patients’ tumors, respectively. Activating mutation in codon 12 and 13 in KRAS was located in the right colon 40.6% vs 25% in the left colon (p=0.130). 64% with KRAS mutation were well or moderately differentiated (p=0,130.). The poorly differentiated amino-acid changes are more frequently observed in codon 12 than in codon 13 and G12D is the most frequent mutation. The second is G12A followed by G12V, G12C and G13D. 18.6% of the patients had MSI-H tumors and four of the tumors MSI-H had activating V600 E BRAF mutation.

Conclusion: Further analyses in larger series are required to confirm these results. Screening program should be set up to determine the incidence rate of the HNPCC which tend to be more frequent in Algeria than in western countries.

Keywords: m CCR Algeria, biomarkers, KRAS, BRAF, MSI, Personalized medicine.