Promoter Methylation Profiles and Its Association with Clinicopathological Features in Breast Cancer

ABSTRACT

PURPOSE: Aberrant DNA methylation of tumor suppressor genes has been accepted as a common feature and early event in human cancer. The aim of this study was to analyze the methylation profiles of 50 well established methylation-associated genes in relation to various clinico-pathological features in breast cancer. METHODS: The methylation status of 50 genes were determined in two breast cancer cell lines, MCF7 and MDA- MB231, using HpaII-MspI-PCR. 8 genes (APC, CALCA, CDH13, MTHFR, S100A2, H19, EDNRB and MUC2) were found to be methylated in at least 1 cell line. The methylation of all 8 genes was observed in tumor tissues, but with different methylation frequencies. RESULTS: The methylation frequencies of five genes in breast cancer were as follows MTHFR (41.9%), APC (51.6%), EDNRB (77.4%), CALCA (80.6%), S100A2 (87.1%), CDH13 (93.5%), H19 (93.5%) and MUC2 (96.8%). The results indicate that a panel of these 8 genes would be useful in the detection of breast cancer. The prognostic significance of DNA methylation in this breast cancer series, the conventional markers of LN status (P=0.05), histologic grade (P= 0.007) and P53 gene status (P=0.049) showed significant prognostic value. CONCLUSION: The methylation of APC, MTHFR, CALCA, CDH13, H19, MUC2, EDNRB and S00A2 would be useful in the detection of breast cancer. Detection of these abnormalities may be useful in the risk assessment and early detection of breast cancer.