KRAS and BRAF Mutations in Patients with Hepatocellular Carcinoma in Senegal

Abstract

Hepatocellular carcinoma (HCC) is a public health problem in developing countries where chronic HBV is endemic. The objective of our study was to determine the prevalence of KRAS and BRAF mutations in patients with HCC. Mutations in codons 12 and 13 of KRAS and the V600E mutation of the BRAF gene were searched by HRM on Light Cycler 480 and confirmed by direct sequencing. A total of 34 HCC patients underwent molecular testing for codon 12 and 13 mutations in the KRAS gene and the V600E mutation in the BRAF gene. Melting curve analysis showed a prevalence of 23.5% (n=8/34) for the KRAS gene and 41.2% (n=14/34) for the BRAF gene. The mean age of BRAF mutation carriers was lower compared with KRAS mutation carriers. Chronic HBV carriage appeared to play a role in the development of these mutations, increasing the risk by 2 (CI(95)=0.55-7.24; p=0.395) for BRAF and by 1.78 (CI(95)=0.23-13.5; p=1) for KRAS. KRAS and BRAF mutations do not appear to play a role in tumor metastasis. However, these results need to be confirmed by further studies with a larger sample size. Alterations in the RAS/RAF/MAP Kinase pathway appear to be more prominent in HBV-induced HCC. This may hinder management with receptor tyrosine kinase inhibitors, the basis for treatment of advanced HCC.