BORIS/CTCFL mRNA isoform expression and epigenetic regulation in epithelial ovarian cancer.
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.
['Link|Petra A|PA|', 'Zhang|Wa|W|', 'Odunsi|Kunle|K|', 'Karpf|Adam R|AR|']
D000077216:Carcinoma, Ovarian Epithelial D019175:DNA Methylation D004268:DNA-Binding Proteins D044127:Epigenesis, Genetic D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D020084:Long Interspersed Nucleotide Elements D008297:Male D008875:Middle Aged D009375:Neoplasms, Glandular and Epithelial D010051:Ovarian Neoplasms D010053:Ovary D020033:Protein Isoforms D012333:RNA, Messenger D013737:Testis
BORIS epigenetics ovarian cancer CTCF DNA methylation