MAPPING OF ER GENE CPG ISLAND METHYLATION BY METHYLATION-SPECIFIC POLYMERASE-CHAIN-REACTION

Southern analysis has shown that DNA from 25% of primary estrogen rece ptor (ER) alpha - negative breast tumors displays aberrant methylation at one site within the ER gene CpG island. To examine more sites and increase sensitivity, we developed a methylation-specific PCR assay to map methylation of the entire ER CpG island. The island was unmethyla ted in normal breast tissue and ER-positive breast cancer cell lines, but extensively methylated in all ER-negative cell lines and breast tu mors examined. In addition, some of the ER-positive/progesterone recep tor-negative and ER-positive/progesterone receptor-positive tumors (ab out 70% and 35%, respectively) displayed methylation of the ER CpG isl and, suggesting that this heterogeneity within tumor cell populations could potentially shed light on the etiology of ER-negative recurrent tumors arising from ER-positive tumors.