Promoter methylation of INK4a/ARF as detected in bile-significance for the differential diagnosis in biliary disease
Détails
ID Serval
serval:BIB_ACBE00D2D751
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Promoter methylation of INK4a/ARF as detected in bile-significance for the differential diagnosis in biliary disease
Périodique
Clinical Cancer Research
ISSN
1078-0432 (Print)
Statut éditorial
Publié
Date de publication
05/2003
Volume
9
Numéro
5
Pages
1773-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Research Support, Non-U.S. Gov't --- Old month value: May
Résumé
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.
Mots-clé
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
Création de la notice
25/01/2008 17:08
Dernière modification de la notice
20/08/2019 16:16