title: 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.
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.
authors.affiliation: Cancer Research UK and University of Edinburgh, Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, Scotland.
authors.forename: C
authors.initials: C
authors.lastname: Gourley
authors.affiliation: Cancer Research UK and University of Edinburgh, Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, Scotland.|Section of Molecular Therapeutics, Department of Cancer Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
authors.forename: A J W
authors.initials: AJW
authors.lastname: Paige
authors.affiliation: Cancer Research UK and University of Edinburgh, Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, Scotland.
authors.forename: K J
authors.initials: KJ
authors.lastname: Taylor
authors.affiliation: Cancer Research UK and University of Edinburgh, Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, Scotland.
authors.forename: D
authors.initials: D
authors.lastname: Scott
authors.affiliation: Cancer Research UK and University of Edinburgh, Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, Scotland.
authors.forename: N-J
authors.initials: NJ
authors.lastname: Francis
authors.affiliation: Cancer Research UK and University of Edinburgh, Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, Scotland.
authors.forename: R
authors.initials: R
authors.lastname: Rush
authors.affiliation: Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Aldaz
authors.affiliation: Cancer Research UK and University of Edinburgh, Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, Scotland.
authors.forename: J F
authors.initials: JF
authors.lastname: Smyth
authors.affiliation: Cancer Research UK and University of Edinburgh, Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, Scotland.|Section of Molecular Therapeutics, Department of Cancer Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
authors.forename: H
authors.initials: H
authors.lastname: Gabra
mesh_terms: D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010053:Ovary / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human