Genomic Instability and Aneuploidy of Hepatocellular Carcinomas (HCC) in Patients with Metabolic Risk Factors

Science Center, Bent Corridor

Hepatocellular carcinomas (HCC) now account for the second highest cancer related death rate in the world. Although common risk factors for HCC include aflatoxin exposure, alcohol abuse and chronic hepatitis, the rise in incidence can be attributed to emerging risk factors such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). It has also been demonstrated that diseases with strong environmental influences such as obesity, metabolic syndrome and diabetes can be contributing factors to the development of NAFLD and NASH. Although HCC’s risk factors are widely understood, little research has been conducted into the heterogeneity of HCC with clinical background of NAFLD or NASH. In order to analyze heterogeneity and clonality of HCC, we have developed a multiplex multi-color Fluorescent in situ Hybridization (FISH) approach that allows the enumeration of 8 distinct gene loci. Using this novel approach we have investigated the evolution of heterogeneity from healthy liver cells to HHC cells. We hope this method of tracking the evolution of NASH and NAFLD to HCC will contribute to the early diagnosis of HCC.