Site-specific CpG methylation in the CCAAT/enhancer binding protein delta (CEBPδ) CpG island in breast cancer is associated with metastatic relapse

• Published in: British journal of cancer 2012-08, Vol.107 (4), p.732-738
• Main Authors: Palmieri, C, Monteverde, M, Lattanzio, L, Gojis, O, Rudraraju, B, Fortunato, M, Syed, N, Thompson, A, Garrone, O, Merlano, M, Lo Nigro, C, Crook, T
• Format: Article
• Language: English
• Subjects: 631/208/2489/2487/2486; 692/699/67/1347; 692/699/67/322; Adult; Aged; Aged, 80 and over; Bioindicators; Biological and medical sciences; Biomarkers; Biomarkers, Tumor - analysis; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast carcinoma; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cancer Research; CCAAT-Enhancer-Binding Protein-delta - genetics; CCAAT/enhancer-binding protein; CpG islands; CpG Islands - genetics; Data processing; DNA; DNA Methylation; Down-Regulation; Drug Resistance; Epidemiology; epigenetics; Female; Genetics and Genomics; genomics; Gynecology. Andrology. Obstetrics; Health risks; Hospitals; Humans; Lesions; Leucine zipper proteins; Mammary gland diseases; Medical research; Medical sciences; Metastases; Metastasis; Middle Aged; Molecular Medicine; Neoplasm Metastasis - genetics; Oncology; Prognosis; Proteins; Recurrence; Transcription factors; Tumor cell lines; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2012.308

Background: The CCAAT/enhancer binding protein delta (CEBP δ ) 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 δ may be involved in the metastatic process. Methods: We analysed the expression of CEBPδ 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 CEBPδ is downregulated in primary breast cancer by site-specific methylation in the CEBPδ CpG island. Expression is also downregulated in 50% of cases during progression from primary carcinoma to metastatic lesions. The CEBPδ CpG island is methylated in 81% metastatic breast cancer lesions, while methylation in the CEBPδ 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 CEBPδ genomic DNA may have utility as an epigenetic biomarker of primary breast carcinomas at increased risk of relapse and metastasis.