Promoter methylation of INK4a/ARF as detected in bile-significance for the differential diagnosis in biliary disease

Details

Serval ID
serval:BIB_ACBE00D2D751
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Promoter methylation of INK4a/ARF as detected in bile-significance for the differential diagnosis in biliary disease
Journal
Clinical Cancer Research
Author(s)
Klump  B., Hsieh  C. J., Dette  S., Holzmann  K., Kiebetalich  R., Jung  M., Sinn  U., Ortner  M., Porschen  R., Gregor  M.
ISSN
1078-0432 (Print)
Publication state
Published
Issued date
05/2003
Volume
9
Number
5
Pages
1773-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Abstract
PURPOSE: There is a need to enhance endobiliary cytotechniques by molecular marker lesions. This is of special significance for patients with primary sclerosing cholangitis, a disease predisposing for the development of cholangiocarcinoma. The INK4a/ADP ribosylation factor (ARF) locus encodes two tumor suppressor genes: p16INK4a and p14ARF. p16INK4a has been shown to be of major significance in cholangiocarcinoma. EXPERIMENTAL DESIGN: In an effort to evaluate the potential diagnostic role of p16INK4a and p14ARF promoter methylation in biliary disease, endoscopical obtained bile specimens of 71 patients were analyzed (26 choledocholithiasis, 6 with normal results, 23 bile duct carcinoma, 5 gall bladder carcinoma). Eleven patients with primary sclerosing cholangitis were enrolled. RESULTS: Merely 6% of specimens (2 of 32) obtained from patients without evidence for malignant biliary disease but 53.5% of malignancies (15 of 28) showed p16 promoter methylation (p14: 3 and 46.2%, respectively). The concordance of methylation rates detected in either bile or tissue specimens was high. In primary sclerosing cholangitis, a similar prevalence of methylation was detected as in malignant disease. CONCLUSIONS: This study demonstrates: (a) a high frequency and specificity of INK4a/ARF methylation in malignant biliary disease compared with mere cholangitis; and (b) the capability to detect these alterations reliably in endoscopically obtained bile. Thus, INK4a/ARF's promoter methylation status represents a candidate marker for the endoscopic diagnosis of biliary disease.
Keywords
Adult Aged Bile Duct Neoplasms/diagnosis/*genetics/metabolism Bile Ducts, Intrahepatic Cholangiocarcinoma/diagnosis/*genetics/metabolism Choledocholithiasis/diagnosis/genetics/metabolism Cyclin-Dependent Kinase Inhibitor p16/*genetics *DNA Methylation DNA, Neoplasm/genetics Diagnosis, Differential Gallbladder Diseases/diagnosis/genetics/metabolism Gene Silencing Humans Middle Aged Prognosis Promoter Regions (Genetics)/*genetics Reverse Transcriptase Polymerase Chain Reaction Survival Rate Tumor Markers, Biological/metabolism Tumor Suppressor Protein p14ARF/*genetics
Pubmed
Web of science
Create date
25/01/2008 16:08
Last modification date
20/08/2019 15:16
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