Analysis of candidate molecular targets in aflatoxin B1-induced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer deaths worldwide. Despite the recent advances in the diagnosis and treatment, HCC still appears to be an important health problem due to the frequency and poor prognosis of the disease. Therefore, understanding its molecular pathogenesis is very important for the development of new diagnostic and therapeutic modalities. Common etiological agents hepatitis B, hepatitis C, aflatoxin B1 (AFB1) and cirrhosis are responsible for about 80% of all HCC cases. Aflatoxins are mycotoxins produced by fungal species in human foods, cereals, feeds and any dried foods at increased humidity and temperature of storage conditions. AFB1 is the best known aflatoxin, which leads to mutations that cause cancer development due to its genotoxic characteristic. The presence of p53 R249S (G>T) mutation is known in AFB1 exposed HCC cases. However, involvement of other pathways or genes accompanying the p53 pathway in the development of AFB1-induced HCC other than this mutation has not been identified yet. In order to define the possible genetic changes taking place before or after the p53 R249S (G>T) mutation, we used two cell lines, MAHLAVU and PLC/PRF both known to carry the R249S mutation. 115 cancer genes previously reported to be involved in carcinogenesis with mutations in different cancer types were analyzed by next generation sequencing technologies. Moreover, BCORL1 and ARID2 genes shown to have mutations in HCC cases resulting from other factors than AFB1 were sequenced by Sanger method. When the results of the two cell lines were compared, no genetic variation possibly associated with AFB1 was detected in the 117 genes.