Pilot Project

Josep Llovet
Josep Llovet, MD
Professor Medicine, Liver Diseases
Mount Sinai School of Medicine

Identification and Treatment of Epigenetic Changes in Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is a devastating disease with complex underlying molecular alterations. Epigenetic changes (DNA hypermethylation / histone modifications) inactivate tumor suppressor genes (TSG) and are of increasing importance for carcinogenesis. Demethylating agents and Histone Deacetylase Inhibitors (HDACi) show first promising results as anticancer treatments and are opening new therapeutic approaches for the management of HCC.

Hypothesis: We postulate that the transcription of several genes in HCC is epigenetically regulated.

Objectives: The overall objective of analyzing methylation changes in HCC is to improve our existing molecular classification and to develop novel treatment strategies.

Preliminary Results: A pilot genome-wide methylation profiling of our Proliferation subclass of HCC was able to discriminate normal liver, cirrhosis and HCC, and identified 3 subgroups, characterized by aberrant methylation.