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rdf:type |
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lifeskim:mentions |
umls-concept:C0012854,
umls-concept:C0017262,
umls-concept:C0023884,
umls-concept:C0086860,
umls-concept:C0185117,
umls-concept:C0332281,
umls-concept:C0345905,
umls-concept:C1419772,
umls-concept:C1512554,
umls-concept:C1517945,
umls-concept:C1520973,
umls-concept:C2911684
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pubmed:issue |
4
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pubmed:dateCreated |
2009-10-15
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pubmed:abstractText |
Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene, localized on 1p36, involved in TGF-beta-Smads signaling. To assess its role in liver fluke-associated intrahepatic cholangiocarcinoma (ICC), the promoter methylation status was investigated in 53 ICCs by methylation-specific PCR, with determination of loss of 1p36.1 by microarray comparative genomic hybridization and RUNX3 protein expression by immunohistochemistry. Loss at 1p36.1 was found 41.5% of ICCs (22/53). In addition, DNA hypermethylation of the RUNX3 promoter was found in 49.1% (26/53) of cancers and 57.1% (4/7) of ICC cell lines. The protein was highly expressed in normal bile ducts but mostly decreased in ICCs, 67.9% (n= 36) being negative for immunohistochemical staining. Promoter hypermethylation of RUNX3 was associated with reversible decrease or absence of RUNX3 protein expression (p<0.001), but this was not found to differ with the ICC subtype. In contrast, loss of 1p36.1 demonstrated a significant link (p= 0.020). In conclusion, RUNX3 promoter hypermethylation and loss of 1p36.1 are causal mechanisms for loss of RUNX3 function in liver fluke-associated ICC carcinogenesis.
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pubmed:language |
eng
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pubmed:journal |
|
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pubmed:citationSubset |
IM
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pubmed:chemical |
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|
pubmed:status |
MEDLINE
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pubmed:issn |
1513-7368
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pubmed:author |
pubmed-author:BanthaisongSS,
pubmed-author:ChewAA,
pubmed-author:DachrutSomkidS,
pubmed-author:HSUF LFL,
pubmed-author:HoCC,
pubmed-author:KosinskiCC,
pubmed-author:PaeyaoAA,
pubmed-author:PairojkulChawalitC,
pubmed-author:PatilM AMA,
pubmed-author:SripaBanchobB,
pubmed-author:SripaMM,
pubmed-author:ZhangJJ
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
575-82
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pubmed:meshHeading |
pubmed-meshheading:19827872-Animals,
pubmed-meshheading:19827872-Antimetabolites, Antineoplastic,
pubmed-meshheading:19827872-Azacitidine,
pubmed-meshheading:19827872-Bile Duct Neoplasms,
pubmed-meshheading:19827872-Bile Ducts, Intrahepatic,
pubmed-meshheading:19827872-Cholangiocarcinoma,
pubmed-meshheading:19827872-Chromosomes, Human, Pair 1,
pubmed-meshheading:19827872-Comparative Genomic Hybridization,
pubmed-meshheading:19827872-Core Binding Factor Alpha 3 Subunit,
pubmed-meshheading:19827872-DNA Methylation,
pubmed-meshheading:19827872-Fasciola hepatica,
pubmed-meshheading:19827872-Fascioliasis,
pubmed-meshheading:19827872-Female,
pubmed-meshheading:19827872-Gene Dosage,
pubmed-meshheading:19827872-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19827872-Humans,
pubmed-meshheading:19827872-Immunoenzyme Techniques,
pubmed-meshheading:19827872-Loss of Heterozygosity,
pubmed-meshheading:19827872-Male,
pubmed-meshheading:19827872-Middle Aged,
pubmed-meshheading:19827872-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:19827872-Polymerase Chain Reaction,
pubmed-meshheading:19827872-Promoter Regions, Genetic
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pubmed:articleTitle |
DNA copy-number loss on 1p36.1 harboring RUNX3 with promoter hypermethylation and associated loss of RUNX3 expression in liver fluke-associated intrahepatic cholangiocarcinoma.
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pubmed:affiliation |
Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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