Journal of Carcinogenesis & Mutagenesis

Abstract

Detection of c-MYC Gene in Micronucleated Hepatocytes from Regenerative Cirrhotic Nodules and Hepatocellular Carcinoma of Hepatitis C Virus Infected Patients

Terezinha Morato Bastos de Almeida, Regina Maria Cubero Leitão, Maisa Yoshimoto, Joyce Anderson Duffles Andrade, Willy Beçak, Flair José Carrilho and Shigueko Sonohara

c-MYC gene alteration has already been shown in chronic liver diseases, which includes hepatocellular carcinoma (HCC). The spontaneous formation of micronucleated hepatocytes (MN-Heps) in liver cirrhosis (LC) tissue from patients infected by hepatitis C virus (HCV), has been previously reported. The objective of this study was to investigate if the c-MYC gene sequence is lost by MN-Heps in cirrhotic process with or without HCC. For this purpose the presence of c-MYC gene in MN-Heps was investigated by fluorescence in situ hybridization in paraffin-embedded liver tissue. Five control liver samples of healthy organ donors were included in this study. Increased c-MYC gene copies were detected in 48-66% of MN-Heps in cirrhotic nodules from all cases, but not in control liver cells. Furthermore, gain of c-MYC gene number of copies was detected in 28% of the hepatocytes from regenerative and macroregenerative nodules (RNs, MRNs). The increase was also determined in 46% of tumor cells. No significant difference in extrusion of the c-MYC gene by RN or MRN hepatocytes was observed. We concluded that RNs and MRNs show cytogenetic abnormality towards the c-MYC gene. Its extrusion in MN-Heps seems to be an early event in regenerative cirrhotic lesions. The increase of c-MYC gene copies in LC from HCV infected patients might contribute to the development of HCC.