Aberrant methylation of APC and RARβ2 genes in breast cancer patients

IUBMB Life. 2015 Jan;67(1):61-8. doi: 10.1002/iub.1346. Epub 2015 Feb 11.

Abstract

Changes in the status of DNA methylation are one of the most common molecular alterations in human neoplasia. We aimed to identify epigenetic molecular markers in serum for early detection of breast cancer. Authors analyzed retrospectively the methylation status of RARβ2 and APC genes in serum samples from 121 breast cancer patients, 79 patients with benign breast diseases, and 66 healthy volunteers using methylation-specific PCR. The methylated APC and RARβ2 were significantly higher in breast cancer patients (93.4%, 95.6%) than benign (7.8%, 14.5%) but not detected in healthy volunteers (0%) at (P < 0.0001). Both methylated genes showed no significant difference among clinicopathological factors apart from triple negative breast cancer patients as all of them (χ(2) = 7.4, P = 0.007) reported to be methylated RARβ2 genes. Both methylated genes were detected in all grades and stages. Both sensitivities and specificities of the methylated genes for breast cancer detection were superior to traditional tumor markers in detection of breast cancer, early stage, low grade tumors, and triple negative breast cancer patients. Thus methylated APC and RARβ2 genes might be valuable serum-based molecular markers for early detection of breast cancer.

Keywords: APC; DNA methylation; breast cancer; early diagnosis RARβ2.

MeSH terms

  • Adenomatous Polyposis Coli Protein / blood
  • Adenomatous Polyposis Coli Protein / metabolism*
  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / physiopathology*
  • DNA Methylation / physiology*
  • DNA Primers / genetics
  • Electrophoresis, Agar Gel
  • Female
  • Humans
  • Middle Aged
  • Polymerase Chain Reaction
  • ROC Curve
  • Receptors, Retinoic Acid / blood
  • Receptors, Retinoic Acid / metabolism*
  • Retrospective Studies

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein
  • Biomarkers, Tumor
  • DNA Primers
  • Receptors, Retinoic Acid
  • retinoic acid receptor, beta2, human