ncer, including EOC, has begun to be more fully appreciated. The most studied epigenetic alteration is DNA methylation, the addition of a methyl moiety to the cytosine-5 position within the context of a CpG dinucleotide, mediated by DNA methyltransferases. DNA methylation patterns are reset early in the embryogenesis and reestablished early during development. After that, they are thought to be relatively stable. In cancer, the physiological regulation of DNA methylation is disrupted leading to drastic changes of the distribution pattern of 5-methylcytosine. The heavy methylation found in the bulk of chromatin is reduced, while the normally unmethylated CpG islands located in the promoter and first exon of genes become hypermethylated. Promoter hypermethylation often leads to inactivation of different tumor-suppressing genes and is associated with many important pathways involved in cancer, such as DNA repair, cell cycle regulation, apoptosis, carcinogen metabolism, hormonal response, and cell adherence. Aberrant DNA methylation is also involved in the development of resistance to chemotherapy . The role of DNA hypomethylation in carcinogenesis is less studied. Recent studies have demonstrated that global decrease in the level of DNA methylation is related to hypomethylation of repeated sequences, increase in genetic instability, as well as reactivation of proto-oncogenes and pro-MEK 162 metastasis genes. Similar to other malignancies, aberrant DNA methylation, including global hypomethylation of heterochromatin and local CpG island methylation, occurs in EOC and contributes to ovarian tumorigenesis and mechanisms of chemoresistance. Applying a more global array-based technology, several studies have demonstrated that DNA methylation changes in ovarian cancer are cumulative with disease progression and CT resistance. Using a similar approach we have recently shown that DNA hypermethylation occurs in less invasive/early stages of ovarian tumorigenesis, while advanced disease was associated with DNA hypomethylation of a number of oncogenes, implicated in cancer progression, invasion/ metastasis and probably chemoresistance. The polypeptide N-acetylgalactosaminyltransferase 3 gene was among the genes identified to be notably hypomethylated in lowmalignant potential and high grade serous EOC tumors. The GALNT3 gene is a member of the GalNAc-transferases gene family; the genes of this family conduct the transfer of N-acetyl galactosamine to the hydroxyl group of a serine or threonine residue in the first step of O-linked oligosaccharide biosynthesis. So far, 20 members of the GALNAC-Ts gene family have been identified and most of them encode an active polypeptide GALNT www.impactjournals.com/oncotarget 545 functioning in the primary step of the O-glycosylation of different proteins, including mucins. Aberrant mucintype O-glycosylation represents one of the most abundant posttranslational cancer-associated changes, comprising diverse biologic and pathologic consequences influencing growth and survival of cancer cells and their ability for invasion and metastasis. The membrane-associated mucin-1, as one highly glycosylated protein, is overexpressed in more than 90% of high-grade PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19858123 EOC tumors including metastatic lesions, as MUC1 expression correlated with EOC progression. This prompted us to further investigate if GALNT3 displays elevated expression levels in serous EOC tumors with different malignant potential, and whether this gene is functionally imp