Loss of heterozygosity and microsatellite instability in human non‐neoplastic hepatic lesions

Abstract

Abstract: Aims/background : Carcinogenesis is thought to be a multistage process that occurs as a result of mutations in oncogenes and tumor suppressor genes. One way to monitor a vast range of these changes is by microsatellite PCR amplification that detects loss of heterozygosity and microsatellite instability between normal and tumor specimens of the same subject. Viral cirrhosis is considered a strong predisposing factor for the development of liver cancer. The aim of the study therefore was to examine precancerous hepatic lesions and compare them with others not considered as high risk for hepatocellular carcinoma. Methods : We examined 43 subjects for 19 microsatellite markers spanning chromosomes 1, 9 and 17. Normal specimens were blood samples that were compared to liver needle biopsies. Samples were classified according to histo‐logical features as non‐cancerous (10 cases) and pre‐cancerous (33 cases, chronic hepatitis and cirrhosis). Results : Our results indicate that there is a tendency of increased chromosomal alteration as lesions become chronic. Samples from patients with antibodies to antibodies for hepatitis C virus show more alterations than hepatitis B positive samples. Stea‐tohepatitis, a disease of unknown etiology, appears to have a high number of microsatellite abnormalities. Conclusions : Microsatellite APOA2 located on chromosome 1, shows a statistically significant increase in the rate of loss of heterozygosity as liver lesions become more severe, indicating the presence of tumor suppressor genes which may be involved in the development of these lesions.