Linked Life Data

15467712

Source:http://linkedlifedata.com/resource/pubmed/id/15467712

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-2-17
pubmed:abstractText
Recent studies indicate that tumor suppressor genes can be epigenetically silenced through promoter hypermethylation. To further understand epigenetic alterations in cholangiocarcinoma, we have studied the methylation profiles of 12 candidate tumor suppressor genes (APC, E-cadherin/CDH1, MGMT, RASSF1A, GSTP, RAR-beta, p14ARF, p15INK4b, p16INK4a, p73, hMLH1 and DAPK) in 72 cases of cholangiocarcinoma, including equal number cases of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma. A total of 10 cases of benign biliary epithelia were included as controls. The methylation status of tumor suppressor genes was analyzed using methylation-specific PCR. We found that 85% of all cholangiocarcinomas had methylation of at least one tumor suppressor gene. The frequency of tumor suppressor gene methylation in cholangiocarcinoma was: RASSF1A (65%), p15INK4b (50%), p16INK4a (50%), APC (46%), E-cadherin/CDH1 (43%), p14(ARF) (38%), p73 (36%), MGMT (33%), hMHL1 (25%), GSTP (14%), RAR-beta (14%) and DAPK (3%). Although single tumor suppressor gene methylation can be seen in benign biliary epithelium, methylation of multiple tumor suppressor genes is only seen in cholangiocarcinoma. About 70% (50/72) of the cholangiocarcinomas had three or more tumor suppressor genes methylated and 52% (38/72) of cases had four or more tumor suppressor genes methylated. Concerted methylation of multiple tumor suppressor genes was closely associated with methylation of RASSF1A, p16 and/or hMHL1. Methylation of RASSF1A was more common in extrahepatic cholangiocarcinoma than intrahepatic cholangiocarcinoma (83 vs 47%, P=0.003) while GSTP was more frequently seen in intrahepatic compared to extrahepatic cholangiocarcinoma (31 vs 6%, P=0.012). Our study indicates that methylation of promoter CpG islands of tumor suppressor genes is a common epigenetic event in cholangiocarcinoma. Based on distinct methylation profiles, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma are two closely related but biologically unique neoplastic processes. Taking advantage of the unique concurrent methylation profile of multiple genes in cholangiocarcinoma may facilitate the distinction of cholangiocarcinoma from benign biliary epithelium in clinical settings.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0893-3952
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
412-20
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma.
pubmed:affiliation
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. yangb@ccf.org
pubmed:publicationType
Journal Article, Comparative Study