Abstract 4103: Hepatocellular carcinoma-specific isoforms of methylated DNA-binding protein 2 and their therapeutic and diagnostic potential

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Liver cancer is the fifth most common cancer in the world. It is particularly prevalent in developing countries in Asia and Africa. In the US alone, it is estimated that 26,190 adults will be diagnosed with primary liver cancer this year, and 19,590 people will die of the disease. Hepatocellular carcinoma has no efficient cure, has a 5-year survival rate of 14% and is highly metastatic. In the last couple of decades, it has been established that many types of cancer involve major changes in the DNA methylation machinery and in turn, widespread yet highly specific changes in cytosine methylation. DNA methylation is a chemical modification on the DNA associated with gene inactivation, and in contrast to genetic mutation, is dynamic and reversible, making it a preferable target for therapeutics. Methylated-DNA Binding Proteins (MBD) have been shown to play a critical role in the progression and metastasis of cancers in general and specifically in hepatocellular carcinoma. We have identified two isoforms of the MBD2 protein (hcMBD2) that have not been previously reported in any somatic cells: these isoforms are totally silenced in normal liver cells and active in hepatocellular carcinoma. Specific inhibition of these isoforms of MBD2 in hepatocellular carcinoma (HePG2 cell line) has a dramatic effect on cell growth and cellular transformation, but no effect in normal cells, where the isoforms are not expressed. Knockdown experiments show dramatic reduction in cell invasiveness, reduced cell growth rate and increased cell death in HepG2 cells, while primary liver hepatocytes remain largely unaffected. A survey of several types of cancers and their surrounding tissue of origin shows the expression of hcMBD2 in several other types of cancer, such as breast cancer. These results position hcMBD as a promising candidate for cancer diagnostics and therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4103. doi:1538-7445.AM2012-4103