Site-specific CpG methylation in the CCAAT/enhancer binding protein delta (CEBP delta) CpG island in breast cancer is associated with metastatic relapse
Abstract
The CCAAT/enhancer binding protein delta (CEBP delta) is a member of a highly conserved family of basic region leucine zipper transcription factors. It has properties consistent with a tumour suppressor; however, other data suggest that CEBP delta may be involved in the metastatic process.
METHODS: We analysed the expression of CEBP delta and the methylation status of the CpG island in human breast cancer cell lines, in 107 archival cases of primary breast cancer and in two series of metastatic breast cancers using qPCR and pyrosequencing. RESULTS: Expression of CEBP delta is downregulated in primary breast cancer by site-specific methylation in the CEBP delta CpG island.
Expression is also downregulated in 50% of cases during progression from primary carcinoma to metastatic lesions. The CEBP delta CpG island is methylated in 81% metastatic breast cancer lesions, while methylation in the CEBP delta CpG island in primary cancers is associated with increased risk of relapse and metastasis.
CONCLUSION: CCAAT/enhancer binding protein delta CpG island methylation is associated with metastasis in breast cancer. Detection of methylated CEBP delta genomic DNA may have utility as an epigenetic biomarker of primary breast carcinomas at increased risk of relapse and metastasis.