RGD Reference Report - APC promoter hypermethylation is an early event in endometrial tumorigenesis. - Rat Genome Database

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APC promoter hypermethylation is an early event in endometrial tumorigenesis.

Authors: Ignatov, Atanas  Bischoff, Joachim  Ignatov, Tanja  Schwarzenau, Christa  Krebs, Thomas  Kuester, Doerthe  Costa, Serban D  Roessner, Albert  Semczuk, Andrzej  Schneider-Stock, Regine 
Citation: Ignatov A, etal., Cancer Sci. 2010 Feb;101(2):321-7. doi: 10.1111/j.1349-7006.2009.01397.x. Epub 2009 Oct 12.
RGD ID: 13524625
Pubmed: PMID:19900189   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1349-7006.2009.01397.x   (Journal Full-text)

The aim of the current study was to investigate the role of promoter methylation of adenomatous polyposis coli (APC) and epithelial cadherin (E-cadherin) genes in endometrial tumorigenesis. The methylation status of both genes was investigated in 43 cases of normal endometrium, 21 simple hyperplasia, 17 atypical hyperplasia, and 86 endometrial carcinoma (EC). Additionally, the methylation pattern of both genes was analyzed in 24 primary ECs and their corresponding metastases. DNA methylation of the APC gene increased from atypical hyperplasia (23.5%) to endometrial carcinoma, reaching its highest level of 77.4% in early stage cancer (FIGO I and II) and decreasing stepwise to 24.2% in advanced stage carcinomas (FIGO III and IV). No methylation of APC was found in normal endometrium or simple hyperplasia. Methylation of E-cadherin was found only in EC (22.1%). The mean age of the patients with aberrant APC methylation was 68.8 years and was significantly higher compared to the mean age (60.9 years) of the patients without methylation of APC promoter (P = 0.02). APC promoter methylation significantly correlated with decreased protein expression of APC (P = 0.039), with increased expression of the Ki-67 proliferative marker (P = 0.006) and decreased metastatic potential (P = 0.002). There was no correlation between APC and E-cadherin methylation patterns and the other clinicopathologic features, nor with patient outcome. Our results suggest that hypermethylation of APC promoter region is an early event in endometrial tumorigenesis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
endometrial carcinoma onsetIAGP 13524625DNA:hypermethylation:promoter: (human)RGD 
endometrial carcinoma onsetISOAPC (Homo sapiens)13524625; 13524625DNA:hypermethylation:promoter: (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Apc  (APC regulator of WNT signaling pathway)

Genes (Mus musculus)
Apc  (APC, WNT signaling pathway regulator)

Genes (Homo sapiens)
APC  (APC regulator of WNT signaling pathway)


Additional Information