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


CONCLUSIONS
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.
Cancer Research UK Laboratories, Imperial Centre for Translational and Experimental Medicine, Division of Cancer, Imperial College London, Du Cane Road, London W12 0NN, UK. c.palmieri@imperial.ac.uk
C
C
Palmieri
M
M
Monteverde
L
L
Lattanzio
O
O
Gojis
B
B
Rudraraju
M
M
Fortunato
N
N
Syed
A
A
Thompson
O
O
Garrone
M
M
Merlano
C
C
Lo Nigro
T
T
Crook
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics*; D011379:Prognosis; D012008:Recurrence
D014408:Biomarkers, Tumor; C497252:CEBPD protein, human; D051743:CCAAT-Enhancer-Binding Protein-delta