BORIS/CTCFL mRNA isoform expression and epigenetic regulation in epithelial ovarian cancer

Petra A. Link, Wa Zhang, Kunle Odunsi, Adam R Karpf

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalCancer Immunity
Volume13
Issue number1
StatePublished - Feb 6 2013

Fingerprint

RNA Isoforms
Epigenomics
Protein Isoforms
Cancer Vaccines
Ovary
Neoplasms
Genomic Imprinting
Antigens
Histone Deacetylase Inhibitors
Neoplasm Genes
DNA Methylation
Ovarian epithelial cancer
Germ Cells
Methylation
Chromatin
Down-Regulation
Cell Line
Messenger RNA
DNA
Pharmaceutical Preparations

Keywords

  • BORIS
  • CTCF
  • DNA methylation
  • Epigenetics
  • Ovarian cancer

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

Cite this

BORIS/CTCFL mRNA isoform expression and epigenetic regulation in epithelial ovarian cancer. / Link, Petra A.; Zhang, Wa; Odunsi, Kunle; Karpf, Adam R.

In: Cancer Immunity, Vol. 13, No. 1, 06.02.2013.

Research output: Contribution to journalArticle

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