RGD Reference Report - DNA methyltransferase 1 expression and promoter methylation of E-cadherin in mucoepidermoid carcinoma. - Rat Genome Database

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DNA methyltransferase 1 expression and promoter methylation of E-cadherin in mucoepidermoid carcinoma.

Authors: Shieh, YS  Shiah, SG  Jeng, HH  Lee, HS  Wu, CW  Chang, LC 
Citation: Shieh YS, etal., Cancer. 2005 Sep 1;104(5):1013-21.
RGD ID: 9588574
Pubmed: PMID:15999364   (View Abstract at PubMed)
DOI: DOI:10.1002/cncr.21278   (Journal Full-text)

BACKGROUND: Loss of E-cadherin expression is found frequently in many types of human malignancies, including mucoepidermoid carcinoma (MEC). CpG methylation in the promoter region has proven important in the regulation of gene expression implicated in malignant transformation. DNA methyltransferases (DNMTs) are the major enzymes involved in establishing genomic methylation patterns. The current study was designed to test the hypothesis that CpG methylation of the promoter region of the E-cadherin gene may inactivate its expression and to examine DNMT 1 (DNMT1) protein expression in MEC. METHODS: Genomic DNA was obtained from paraffin embedded sections by laser microdissection in 46 MEC specimens. Methylation status of the E-cadherin promoter was examined by utilizing the methylation-specific polymerase chain reaction assay. To examine E-cadherin and DNMT1 proteins expression levels, the MEC specimens and adjacent epithelial tissues were studied immunohistochemically. Chi-square analysis was used to evaluate the correlation of protein expression and E-cadherin methylation status with clinicopathologic parameters. Comparisons of the survival rate between patients with DNMT1-positive and DNMT1-negative patients were made using Kaplan-Meier analysis. RESULTS: The data showed that all normal tissues expressed E-cadherin, and no promoter methylation was detected. Of the MEC samples analyzed, methylation allele was found in 33 of 46 samples (72%), and reduced E-cadherin expression was found in 21 of 46 samples (45%). DNMT1-positive expression was observed in 29 of 46 MEC samples (63%). A significant correlation was found between E-cadherin expression and the methylation status of E-cadherin promoter (P = 0.021). In addition, increased DNMT1 expression was correlated with histologic grade, clinical stage, and a poor prognosis in patients with MEC. CONCLUSIONS: Hypermethylation of CpG sites at the 5' promoter of E-cadherin was a common event associated with E-cadherin expression levels in MEC, suggesting an epigenetically mediated loss of E-cadherin function in these tumors. Increased DNMT1 protein expression may play a critical role in the carcinogenesis and disease progression of MEC.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CDH1Humanmucoepidermoid carcinoma  IDA DNA:hypermethylation:promoter:RGD 
Cdh1Ratmucoepidermoid carcinoma  ISOCDH1 (Homo sapiens)DNA:hypermethylation:promoter:RGD 
Cdh1Mousemucoepidermoid carcinoma  ISOCDH1 (Homo sapiens)DNA:hypermethylation:promoter:RGD 
DNMT1Humanmucoepidermoid carcinoma disease_progressionIEP  RGD 
Dnmt1Ratmucoepidermoid carcinoma disease_progressionISODNMT1 (Homo sapiens) RGD 
Dnmt1Mousemucoepidermoid carcinoma disease_progressionISODNMT1 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cdh1  (cadherin 1)
Dnmt1  (DNA methyltransferase 1)

Genes (Mus musculus)
Cdh1  (cadherin 1)
Dnmt1  (DNA methyltransferase 1)

Genes (Homo sapiens)
CDH1  (cadherin 1)
DNMT1  (DNA methyltransferase 1)


Additional Information