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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2003-7-22
pubmed:abstractText
To investigate the relationship between DNA hypomethylation and gene overexpression in pancreatic cancer, we analyzed the methylation status of a subset of 18 genes previously identified by global gene expression studies as overexpressed in pancreatic cancer tissues compared with normal pancreas. For comparison, we determined the methylation status of 14 genes not known to be overexpressed in pancreatic cancer. Methylation-specific PCR analysis revealed that 19 of these 32 genes were methylated at their 5' CpGs in normal pancreas. We then analyzed these 19 genes for their methylation pattern in pancreatic cancers and found that all 7 of the genes (claudin4, lipocalin2, 14-3-3sigma, trefoil factor2, S100A4, mesothelin, and prostate stem cell antigen) that were overexpressed in the neoplastic cells of pancreatic cancers and not expressed in normal pancreatic duct displayed a high prevalence of hypomethylation in pancreatic cancer cell lines and primary pancreatic carcinomas. By contrast, only 1 of 12 genes not overexpressed in pancreatic cancer demonstrated hypomethylation (P = 0.0002). In pancreatic cancer cell lines that retained methylation of 1 or more of the 7 aforementioned overexpressed and hypomethylated genes, treatment with 5-aza-2'-deoxycytidine or with trichostatin A, either alone or in combination, almost invariably reactivated the transcription of each of these 7 genes. These results indicate that gene hypomethylation is a frequent epigenetic event in pancreatic cancer and is commonly associated with the overexpression of affected genes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4158-66
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Frequent hypomethylation of multiple genes overexpressed in pancreatic ductal adenocarcinoma.
pubmed:affiliation
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't