Cancer germline (CG) genes are normally expressed in germ cells and aberrantly 
expressed in a variety of cancers; their immunogenicity has led to the 
widespread development of cancer vaccines targeting these antigens. BORIS/CTCFL 
is an autosomal CG antigen and promising cancer vaccine target. BORIS is the 
only known paralog of CTCF, a gene intimately involved in genomic imprinting, 
chromatin insulation, and nuclear regulation. We have previously shown that 
BORIS is expressed in epithelial ovarian cancer (EOC) and that its expression 
coincides with promoter and global DNA hypomethylation. Recently, 23 different 
BORIS mRNA variants have been described, and have been functionally grouped into 
six BORIS isoform families (sf1-sf6). In the present study, we have 
characterized the expression of BORIS isoform families in normal ovary (NO) and 
EOC, the latter of which were selected to include two groups with widely varying 
global DNA methylation status. We find selective expression of BORIS isoform 
families in NO, which becomes altered in EOC, primarily by the activation of 
BORIS sf1 in EOC. When comparing EOC samples based on methylation status, we 
find that BORIS sf1 and sf2 isoform families are selectively activated in 
globally hypomethylated tumors. In contrast, CTCF is downregulated in EOC, and 
the ratio of BORIS sf1, sf2, and sf6 isoform families as a function of CTCF is 
elevated in hypomethylated tumors. Finally, the expression of all BORIS isoform 
families was induced to varying extents by epigenetic modulatory drugs in EOC 
cell lines, particularly when DNMT and HDAC inhibitors were used in combination.