WWOX mRNA expression profile in epithelial ovarian cancer supports the role of WWOX variant 1 as a tumour suppressor, although the role of variant 4 remains unclear

C Gourley, A J W Paige, K J Taylor, D Scott, N-J Francis, R Rush, C M Aldaz, J F Smyth, H Gabra

Research output: Contribution to journalArticlepeer-review

Abstract

WWOX is a candidate tumour suppressor gene that exhibits LOH or homozygous deletion in several tumour types. As well as the predominant full-length transcript (variant 1) there also exist alternatively spliced transcripts found previously only in malignant tissue. It has been suggested that proteins encoded by these variants may interfere with normal WWOX function in a dominant negative fashion. The most prevalent alternate transcript demonstrated in ovarian cancer is variant 4, which lacks exons 6-8. Here, we report the first comparison of the mRNA expression of WWOX variants 1 and 4 in human ovarian tumours and normal ovaries, and correlate expression with clinical data. We demonstrate significantly lower WWOX variant 1 expression in tumours than in normal ovaries. This reduction was not associated with any specific clinical subgroup. Variant 4 was expressed at low levels, and significantly associated with high grade and advanced stage ovarian cancer. Furthermore, tumours co-expressing variant 4 and relatively high levels of variant 1 showed significantly worse survival than tumours expressing variant 1 alone. However, variant 4 was also frequently identified in non-malignant ovarian tissue. These results support the role of WWOX variant 1 as a suppressor of ovarian tumourigenesis, but the role of variant 4 remains speculative.
Original languageEnglish
Pages (from-to)1681-9
Number of pages9
JournalInternational journal of oncology
Volume26
Issue number6
Publication statusPublished - Jun 2005

Keywords

  • Female
  • Gene Expression Profiling
  • Genes, Tumor Suppressor
  • Humans
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms
  • Ovary
  • Oxidoreductases
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Proteins

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