We assessed expression of the BRCA1, CTCF and DNMT3b methyltransferase genes 
along with BRCA1 promoter methylation to better define the epigenetic events 
involved in BRCA1 inactivation in sporadic breast cancer. These gene expression 
patterns were determined in 54 sporadic breast tumours by immunohistochemistry 
and the methylation status of the BRCA1 promoter was evaluated using 
methylation-specific PCR. We observed significant DNMT3b expression in 80% of 
the tumours and that 43% of tumours exhibited novel cytoplasmic CTCF expression. 
Pairwise analyses of gene expression patterns showed that 28/32 tumours lacked 
BRCA1 expression and also exhibited cytoplasmic CTCF staining, while 24/32 of 
these tumours also overexpressed DNMT3b. Furthermore, 86% of the BRCA1 
low-expressing tumours were methylated at the BRCA1 promoter and a subset of 
these tumours displayed both cytoplasmic CTCF and increased DNMT3b expression. 
Thus, tumour subsets exist that display concurrent decreased BRCA1 expression, 
BRCA1 promoter methylation, cytoplasmic CTCF expression and with DNMT3b 
over-expression. We suggest that these altered CTCF and DNMT3b expression 
patterns represent (a) critical events responsible for the epigenetic 
inactivation of BRCA1 and (b) a diagnostic signature for epigenetic inactivation 
of other tumour suppressor genes in sporadic breast tumours.