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

نویسندگان

  • Bodo Klump
  • Chih-Jen Hsieh
  • Stephan Dette
  • Karlheinz Holzmann
  • Ralf Kiebetalich
  • Michael Jung
  • Udo Sinn
  • Marianne Ortner
  • Rainer Porschen
  • Michael Gregor
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

INK4a-ARF alterations in liver cell adenoma.

BACKGROUND The INK4a-ARF (CDKN2A) locus on chromosome 9p21 encodes two tumour suppressor proteins, p16(INK4a) and p14(ARF), whose functions are inactivated in many human cancers. AIMS To evaluate p14(ARF) and p16(INK4a) alterations in liver cell adenoma. METHODS After microdissection, DNA from 25 liver cell adenomas and corresponding normal liver tissue were analysed for INK4-ARF inactivati...

متن کامل

Morphologically normal-appearing mammary epithelial cells obtained from high-risk women exhibit methylation silencing of INK4a/ARF.

PURPOSE p16(INK4a) has been appreciated as a key regulator of cell cycle progression and senescence. Cultured human mammary epithelial cells that lack p16(INK4a) activity have been shown to exhibit premalignant phenotypes, such as telomeric dysfunction, centrosomal dysfunction, a sustained stress response, and, most recently, a dysregulation of chromatin remodeling and DNA methylation. These da...

متن کامل

Detection of Helicobacter DNA in Bile Samples of Patients with Biliary Diseases Living in South of Iran

Background: It has been reported that several species of Helicobacter colonize the biliary tract of animals and human, but their participation in hepatobiliary diseases are not established. This study is undertaken to determine if Helicobacter genus members, especially with regard to H. pylori, could be detected in the bile and gallbladder diseases. Methods: Thirty-eight gallbladder tissues and...

متن کامل

The Frequency of Bacterial Agents in the Bile Juice of Patients with Bile Stones and Biliary Disorders

Abstract Background and objectives: Bile in healthy people is a sterile fluid and presence of any microorganism can be a marker for a disorder like cholelithiasis. The aim of this study was to determine the frequency of bacterial agents in the bile of patients with bilestone, malignant pancreatic and biliary diseases. Material and Methods: One hundred and two bile samples were obtained, during ...

متن کامل

Study of the role of siRNA mediated promoter methylation in DNMT3B knockdown and alteration of promoter methylation of CDH1, GSTP1 genes in MDA-MB -453 cell line

Promoter methylation is one of the main epigenetic mechanisms that lead to the inactivation of tumor suppressor genes during carcinogenesis. Due to the reversible nature of DNA methylation, many studies have been performed to correct theses epigenetic defects by inhibiting DNA methyltransferases (DNMTs). In this case novel therapeutics especially siRNA oligonucleotides have been used to specifi...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Clinical cancer research : an official journal of the American Association for Cancer Research

دوره 9 5  شماره 

صفحات  -

تاریخ انتشار 2003