We performed a global methylation profiling assay on 1505 CpG sites across 807 genes to characterize DNA methylation patterns in pancreatic cancer genome. We found 289 CpG sites that were differentially methylated in normal pancreas, pancreatic tumors and cancer cell lines. We identified 23 and 35 candidate genes that are regulated by hypermethylation and hypomethylation in pancreatic cancer, respectively. We also identified candidate methylation markers that alter the expression of genes critical to gemcitabine susceptibility in pancreatic cancer. These results indicate that aberrant DNA methylation is a frequent epigenetic event in pancreatic cancer; and by using global methylation profiling assay, it is possible to identify these markers for diagnostic and therapeutic purposes in this disease. Published by Elsevier B.V. All rights reserved. Cancer is a complex disease characterized by multiple genetic and epigenetic genomic alterations (Esteller, 2007; Feinberg et al., 2006; Jones and Baylin, 2002) . DNA methylation is one of the most important epigenetic alterations and plays a critical functional role in development, differentiation and diseases (Jones and Baylin, 2002) . Through the activity of DNA methyltransferases (DNMTs), DNA methylation occurs at the cytosine residue in the context of 5 0 -CG-3 0 (CpG dinucleotide) across human genome (Laird, 2003) . During the developmental process, DNA methylation plays an essential role in X chromosome inactivation in female somatic cells and in the mono-allelic silencing of parentally imprinted genes (Herman and Baylin, 2003) . Once these DNA methylation patterns are acquired in the early embryo stage, these patterns are inherited and maintained in successive cell generations. Promoter regions are usually enriched with CpG dinucleotides, known as CpG islands; and hypermethylation of these islands correlates with transcriptional silencing of tumor suppressor genes (Herman and Baylin, 2003) . Conversely, increased expressions of oncogenes were associated with hypomethylation (Cui et al., 2002) . This hypomethylation is known to contribute to cancer cell phenotypes through loss of imprinting (LOI) and genomic instability that characterizes tumors (Cui et al., 2002) . Furthermore, tumorigenesis of several cancers was also marked by specific methylation changes in their genomes (Yegnasubramanian et al., 2004) . Therefore, it is useful to construct a global methylation profile to discover candidate genes and to predict
Tan et al. REF indicated that aberrant DNA methylation is a frequent epigenetic event in pancreatic cancer.
Characterizing DNA methylation patterns in pancreatic cancer genome.
Molecular oncology
Molecular oncology
Medicine Biology