ABSTRACT
Epigenetic changes play a major role in the initiation and progression of human cancer, in addition to genetic alterations. Overall, the genome of tumor cells is characterized by global CpG dinucleotide hypomethylation and reductions of specific histone modifications, i.e., loss of monoacetylation at lysine 16 and trimethylation at lysine 20 of histone H4 [1,2]. These global epigenetic alterations are thought to contribute to carcinogenesis through harmful expression of inserted viral sequences, oncogene activation, loss of imprinting and X chromosome inactivation, and genomic instability through hypomethylation of structural elements. On the other hand, promoter hypermethylation and deacetylation of CpG islands of tumor suppressor genes results in aberrant transcriptional silencing [3]. Many genes, located across all chromosome locations, are epigenetically silenced in cancer cells, of which some methylated genes are shared and others are tumortype-specific. Examples are genes involved in cell cycle regulation and apoptosis (p14ARF, p15INK4b, p16INK4a, APC, RASSF1A, HIC1), DNA repair genes (hMLH1, GSTP1, MGMT, BRCA1), and genes related to metastasis and invasion (CDH1, TIMP-3, DAPK, p73, maspin, TSP1, VHL) [4].
