[Promoter methylation of ID4. A marker for recurrence-free survival in human breast cancer].
The aim of this study was to unravel the role of the transcription factor inhibitor of DNA binding 4 (ID4) in human breast carcinogenesis in more detail, especially the impact of ID4 promoter methylation on disease progression. Demethylating treatment of breast cancer cell lines was associated with ID4 reexpression. ID4 promoter methylation was frequently observed in primary breast cancer samples (68.9%, 117/170). We found a very tight correlation (p<0.001) between ID4 promoter methylation and loss of ID4 mRNA expression in these specimens. For breast tissue as the first tumour entity analyzed in detail, we could show a direct correlation between ID4 promoter methylation and loss of ID4 expression on both the mRNA and protein level. Interestingly, ID4 promoter methylation was a factor for unfavourable recurrence-free survival (p=0.036) and increased the patient's risk for lymph node metastases (p=0.030). Our data suggest that ID4 is a potential tumour suppressor gene in human breast tissues that undergoes epigenetic silencing during carcinogenesis, leading to an increased risk for tumour relapse. Thus, ID4 methylation status could serve as a prognostic biomarker in human breast cancer.
Noetzel
E
E
Arbeitsgruppe Molekulare Onkologie, Institut für Pathologie, Universitätsklinikum Aachen.
Veeck
J
J
Horn
F
F
Hartmann
A
A
Knüchel
R
R
Dahl
E
E
D014408:Biomarkers, Tumor / Q000235:genetics*; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics*; D008207:Lymphatic Metastasis / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D047368:Tumor Burden
D014408:Biomarkers, Tumor; C490128:ID4 protein, human; D051796:Inhibitor of Differentiation Proteins