RGD Reference Report - Promoter hypermethylation of DAP-kinase is associated with poor survival in primary biliary tract carcinoma patients. - Rat Genome Database

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Promoter hypermethylation of DAP-kinase is associated with poor survival in primary biliary tract carcinoma patients.

Authors: Tozawa, T  Tamura, G  Honda, T  Nawata, S  Kimura, W  Makino, N  Kawata, S  Sugai, T  Suto, T  Motoyama, T 
Citation: Tozawa T, etal., Cancer Sci. 2004 Sep;95(9):736-40.
RGD ID: 2324957
Pubmed: PMID:15471559   (View Abstract at PubMed)

To clarify the clinicopathological significance of promoter hypermethylation of tumor suppressor and tumor-related genes in biliary tract carcinomas, we examined the promoter methylation status of multiple genes in primary biliary tract carcinomas. These consisted of carcinomas of the bile duct, gallbladder, and duodenal ampulla. Surgical specimens were obtained from a total of 37 patients with biliary tract carcinoma. The cohort consisted of 23 patients with bile duct carcinoma, 9 patients with gallbladder carcinoma, and 5 patients with ampullary carcinoma. The methylation status of CHFR, DAP-kinase, E-cadherin, hMLH1, p16, RASSF1A, and RUNX3 was examined by methylation-specific polymerase chain reaction (MSP). The correlation between methylation status and clinicopathological characteristics was then assessed. The methylation frequencies of CHFR, DAP-kinase, E-cadherin, hMLH1, p16, RASSF1A, and RUNX3 genes were 16.2%, 21.4%, 27.0%, 8.1%, 24.3%, 27.0%, and 56.8%, respectively, in primary biliary tract carcinomas. The number of methylated genes per sample was 2.17 +/- 0.28 (average +/- SD) in bile duct carcinomas, 1.80 +/- 0.97 in ampullary carcinomas, and 0.89 +/- 0.35 in gallbladder carcinomas, with a statistically significant difference between bile duct carcinomas and gallbladder carcinomas (P = 0.02). As for clinicopathological significance, patients with a methylated RUNX3 promoter were significantly older than those with unmethylated RUNX3 (P = 0.01), and DAP-kinase methylation was more frequent in poorly differentiated tumors than in well to moderately differentiated ones (P = 0.04). The overall survival rate was significantly lower in patients with methylated DAP-kinase (P = 0.009) or RUNX3 (P = 0.034) compared to those with unmethylated genes. Furthermore, DAP-kinase methylation-positive status was independently associated with poor survival in multivariate analyses (hazard ratio = 8.71, P = 0.024). A significant proportion of primary biliary tract carcinomas exhibited promoter hypermethylation of tumor suppressor and tumor-related genes, although bile duct carcinomas are more prone to being affected by promoter methylation than are gallbladder carcinomas. Hypermethylation of DAP-kinase appears to be a significant prognostic factor in primary biliary tract carcinomas.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Bile Duct Neoplasms  IDA 2324957DNA:hypermethylation:promoterRGD 
Bile Duct Neoplasms  ISORUNX3 (Homo sapiens)2324957; 2324957DNA:hypermethylation:promoterRGD 
Digestive System Neoplasms  IDA 2324957DNA:hypermethylation:promoterRGD 
Digestive System Neoplasms  ISORUNX3 (Homo sapiens)2324957; 2324957DNA:hypermethylation:promoterRGD 
Gallbladder Neoplasms  IDA 2324957DNA:hypermethylation:promoterRGD 
Gallbladder Neoplasms  ISORUNX3 (Homo sapiens)2324957; 2324957DNA:hypermethylation:promoterRGD 

Objects Annotated

Genes (Rattus norvegicus)
Runx3  (RUNX family transcription factor 3)

Genes (Mus musculus)
Runx3  (runt related transcription factor 3)

Genes (Homo sapiens)
RUNX3  (RUNX family transcription factor 3)


Additional Information