title: Assessment of DNA methylation status in early stages of breast cancer development.
abstract: BACKGROUND
  Molecular pathways determining the malignant potential of premalignant breast lesions remain unknown. In this study, alterations in DNA methylation levels were monitored during benign, premalignant and malignant stages of ductal breast cancer development.
  
  
  METHODS
  To study epigenetic events during breast cancer development, four genomic biomarkers (Methylated-IN-Tumour (MINT)17, MINT31, RARβ2 and RASSF1A) shown to represent DNA hypermethylation in tumours were selected. Laser capture microdissection was employed to isolate DNA from breast lesions, including normal breast epithelia (n=52), ductal hyperplasia (n=23), atypical ductal hyperplasia (n=31), ductal carcinoma in situ (DCIS, n=95) and AJCC stage I invasive ductal carcinoma (IDC, n=34). Methylation Index (MI) for each biomarker was calculated based on methylated and unmethylated copy numbers measured by Absolute Quantitative Assessment Of Methylated Alleles (AQAMA). Trends in MI by developmental stage were analysed.
  
  
  RESULTS
  Methylation levels increased significantly during the progressive stages of breast cancer development; P-values are 0.0012, 0.0003, 0.012, <0.0001 and <0.0001 for MINT17, MINT31, RARβ2, RASSF1A and combined biomarkers, respectively. In both DCIS and IDC, hypermethylation was associated with unfavourable characteristics.
  
  
  CONCLUSIONS
  DNA hypermethylation of selected biomarkers occurs early in breast cancer development, and may present a predictor of malignant potential.
authors: Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, CA 90404, USA.
authors: A Q
authors: AQ
authors: van Hoesel
authors: Y
authors: Y
authors: Sato
authors: D A
authors: DA
authors: Elashoff
authors: R R
authors: RR
authors: Turner
authors: A E
authors: AE
authors: Giuliano
authors: J M
authors: JM
authors: Shamonki
authors: P J K
authors: PJ
authors: Kuppen
authors: C J H
authors: CJ
authors: van de Velde
authors: D S B
authors: DS
authors: Hoon
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061346:Laser Capture Microdissection; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D013997:Time Factors
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