HEPATOLOGY: Genetic and epigenetic alterations of the KLF6 gene in hepatocellular carcinoma

Background and Aim:Kruppel-like factor 6 (KLF6) is a zinc finger tumor suppressor gene that is frequently mutated in several human cancers and is broadly involved in differentiation and development, growth-related signal transduction, cell proliferation, apoptosis, and angiogenesis. The aim of this study was to elucidate the potential etiological role of KLF6 in the development of hepatocellular carcinoma (HCC) in Korea. Methods:The gene mutation, allelic loss, and methylation status of the KLF6 gene was analyzed in a series of 85 Korean patients: 21 with dysplastic nodules and 85 with HCC. Results:No somatic mutations were observed in the patients with dysplastic nodules or with HCC. Allelic loss was found in five (6.8%) of 73 informative HCC tissues. Three of the five patients with allelic loss had HCC with hepatitis B virus infection and cirrhosis, and the remaining two had no viral infection and a non-specific background. In methylation analysis, unmethylated and methylated DNAs of the KLF6 gene were amplified in all corresponding non-neoplastic liver tissues. Only one HCC tissue showed methylated DNA without unmethylated DNA. Conclusions:The results suggest that genetic and epigenetic alteration of KLF6 may play a minor role in the development of HCC.