Gene Promoter Hypermethylation in Tumors and Plasma of Breast Cancer Patients

Bae, Young-Kyung;Shim, Young-Ran;Choi, Joon-Hyuk;Kim, Mi-Jin;Edward, Gabrielson;Lee, Soo-Jung;Hwang, Tae-Yoon;Shin, Sei-One

  • Published : 20050800

Abstract

Purpose: To measure the hypermethylation of four enes 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 $\beta$ (RAR$\beta$), 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%), RAR$\beta$ (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 RAR$\beta$, 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.

Keywords

References

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