Evaluation of CTNNB1, TP53, and hTERT promoter variability in patients with hepatocellular carcinoma

Hepatocellular carcinoma (HCC) remains one of the most challenging health problems worldwide. Currently, HCC is the fifth most common cancer, and the second leading cause of cancer-related death globally. Although HCC is more prevalent in Asian and African nations, important evidence indicates that the incidence of HCC is rising in developed countries. Various risk factors for HCC development are well defined, such as hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection, cirrhosis (that is, chronic liver damage caused by inflammation and fibrosis) alcohol abuse and metabolic syndrome. Other cofactors such as tobacco use and intake of aflatoxin B1 (a fungal carcinogen present in food supplies associated with mutations in the tumor suppressor gene TP53) are wellcharacterized contributors to HCC. However, the exact molecular mechanisms underlying the development of HCC are still unclear. Over the past decade, there has been an improvement in the understanding of the molecular pathogenesis of HCC. Genomic analyses have provided a clear picture of the main drivers responsible for tumor initiation and progression. Each HCC has an average of 40 genomic aberrations, among which few are considered drivers. The most frequent mutations are able to affect WNT–β-catenin pathway activation (because of mutations in β-catenin, encoded by CTNNB1 gene), functions of the cellular tumour antigen p53 (encoded by TP53 gene), and telomere maintenance (because of mutations in telomere reverse transcriptase, encoded by TERT gene).A recent study has shown that occurrence of somatic mutations in CTNNB1 and TP53 genes is a rare event in HCC patients from Southern Italy. Indeed, no CTNNB1 exon 3 mutations or TP53 mutations were detected in any case. The aim of this study was to investigate genetic heterogeneity of CTNNB1, TP53, and hTERT promoter in paired tumorous and nontumorous liver specimens of a large cohort of patients with HCC from Southern Italy.