Cancer Res Treat.  2005 Aug;37(4):233-240.

Gene Promoter Hypermethylation in Tumors and Plasma of Breast Cancer Patients

Affiliations
  • 1Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea. ykbae@yumail.ac.kr
  • 2Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea.
  • 3Department of Preventive Medicine and Public Health, Yeungnam University College of Medicine, Daegu, Korea.
  • 4Department of Radiation Oncology, Yeungnam University College of Medicine, Daegu, Korea.
  • 5Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

PURPOSE
To measure the hypermethylation of four genes in primary tumors and paired plasma samples to determine the feasibility of gene promoter hypermethylation markers for detecting breast cancer in the plasma. MATERIALS AND METHODS: DNA was extracted from the tumor tissues and peripheral blood plasma of 34 patients with invasive breast cancer, and the samples examined for aberrant hypermethylation in cyclin D2, retinoic acid receptor beta (RARbeta), twist and high in normal-1 (HIN-1) genes using methylation-specific PCR (MSP), and the results correlated with the clinicopathological parameters. RESULTS: Promoter hypermethylation was detected at high frequency in the primary tumors for cyclin D2 (53%), RARbeta (56%), twist (41%) and HIN-1 (77%). Thirty-three of the 34 (97%) primary tumors displayed promoter hypermethylation in at least one of the genes examined. The corresponding plasma samples showed hyperme thylation of the same genes, although at lower frequencies (6% for cyclin D2, 16% for RARbeta, 36% for twist, and 54% for HIN-1). Overall, 22 of the 33 (67%) primary tumors with hypermethylation of at least one of the four genes also had abnormally hypermethylated DNA in their matched plasma samples. No significant relationship was recognized between any of the clinical or pathological parameters (tumor size, axillary lymph node metastasis, stage, or Ki-67 labeling index) with the frequency of hypermethylated DNA in the primary tumor or plasma. CONCLUSION: The detection of aberrant promoter hypermethylation of cancer-related genes in the plasma may be a useful tool for the detection of breast cancer.

Keyword

Methylation; Plasma; Breast neoplasms

MeSH Terms

Breast Neoplasms*
Breast*
Cyclin D2
DNA
Humans
Lymph Nodes
Methylation
Neoplasm Metastasis
Plasma*
Polymerase Chain Reaction
Receptors, Retinoic Acid
Cyclin D2
DNA
Receptors, Retinoic Acid
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