title: Epigenetic changes associated with neoplasms of the exocrine and endocrine pancreas.
abstract: Early detection and multi-modality curative treatment for pancreatic cancer remain unsatisfactory due to the insufficient understanding of the mechanisms underlying tumor progression. Epigenetic events, including aberrant methylation of tumor suppressor gene promoter regions, may contribute to tumorigenesis involving both the exocrine and endocrine pancreas. Methylation changes of specific gene promoter regions were examined in 48 resected neoplasms of the exocrine and endocrine pancreas, which were obtained as paraffin-embedded tissue samples. The pancreatic neoplasms included acinar cell carcinoma (n=12), adenocarcinoma (n=18), and islet cell tumors (n=18). DNA methylation was determined with a nested methylation-specific PCR (MSP) technique incorporating an initial bisulfite modification of tumor DNA for the promoter regions associated with 14 tumor suppressor genes. In decreasing order, the 6 most frequently methylated genes were: APC 50%, BRCA1 46%, p16INK4a 35%, p15INK4b 35%, RARβ 35%, and p73 33%. Overall, 94% of the tumors had methylation of at least one gene, and methylation of two or more genes was present in 69% of pancreatic tumors. Pancreatic adenocarcinomas had patterns of gene methylation that differed from pancreatic endocrine tumors. These differences were most notable for the APC and hMLH1 genes.
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Jia
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Yu
authors.forename: Michael G
authors.initials: MG
authors.lastname: House
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.forename: Malcolm V
authors.initials: MV
authors.lastname: Brock
authors.forename: James G
authors.initials: JG
authors.lastname: Herman
mesh_terms: D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D046790:Pancreas, Exocrine / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics