Alterations in the common fragile site gene Parkin in ovarian and other cancers

Stacy R. Denison, Fang Wang, Nicole A. Becker, Birgitt Schüle, Norman Kock, Leslie A. Phillips, Christine Klein, David I. Smith

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

The cloning and characterization of the common fragile site (CFS) FRA6E (6q26) identified Parkin, the gene involved in the pathogenesis of many cases of juvenile, early-onset and, rarely, late-onset Parkinson's disease, as the third large gene to be localized within a large CFS. Initial analyses of Parkin indicated that in addition to playing a role in Parkinson's disease, it might also be involved in the development and/or progression of ovarian cancer. These analyses also indicated striking similarities among the large CFS-locus genes: fragile histidine triad gene (FHIT; 3p14.2), WW domain-containing oxidoreductase gene (WWOX; 16q23), and Parkin (6q26). Analyses of FHIT and WWOX in a variety of different cancer types have identified the presence of alternative transcripts with whole exon deletions. Interestingly, various whole exon duplications and deletions have been identified for Parkin in juvenile and early-onset Parkinson's patients. Therefore, we performed mutational/exon rearrangement analysis of Parkin in ovarian cancer cell lines and primary tumors. Four (66.7%) cell lines and four (18.2%) primary tumors were identified as being heterozygous for the duplication or deletion of a Parkin exon. Additionally, three of 23 (13.0%) nonovarian tumor-derived cell lines were also identified as having a duplication or deletion of one or more Parkin exons. Analysis of Parkin protein expression with antibodies revealed that most of the ovarian cancer cell lines and primary tumors had diminished or absent Parkin expression. While functional analyses have not yet been performed for Parkin, these data suggest that like FHIT and WWOX, Parkin may represent a tumor suppressor gene.

Original languageEnglish (US)
Pages (from-to)8370-8378
Number of pages9
JournalOncogene
Volume22
Issue number51
DOIs
StatePublished - Nov 13 2003

Fingerprint

Ovarian Neoplasms
Exons
Tumor Cell Line
Genes
Parkinson Disease
Tumor Suppressor Genes
Histidine
Organism Cloning
Neoplasms
Oxidoreductases
Cell Line
Antibodies

Keywords

  • Common fragile sites
  • Ovarian cancer
  • Parkinson's disease

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Denison, S. R., Wang, F., Becker, N. A., Schüle, B., Kock, N., Phillips, L. A., ... Smith, D. I. (2003). Alterations in the common fragile site gene Parkin in ovarian and other cancers. Oncogene, 22(51), 8370-8378. https://doi.org/10.1038/sj.onc.1207072

Alterations in the common fragile site gene Parkin in ovarian and other cancers. / Denison, Stacy R.; Wang, Fang; Becker, Nicole A.; Schüle, Birgitt; Kock, Norman; Phillips, Leslie A.; Klein, Christine; Smith, David I.

In: Oncogene, Vol. 22, No. 51, 13.11.2003, p. 8370-8378.

Research output: Contribution to journalArticle

Denison, SR, Wang, F, Becker, NA, Schüle, B, Kock, N, Phillips, LA, Klein, C & Smith, DI 2003, 'Alterations in the common fragile site gene Parkin in ovarian and other cancers', Oncogene, vol. 22, no. 51, pp. 8370-8378. https://doi.org/10.1038/sj.onc.1207072
Denison SR, Wang F, Becker NA, Schüle B, Kock N, Phillips LA et al. Alterations in the common fragile site gene Parkin in ovarian and other cancers. Oncogene. 2003 Nov 13;22(51):8370-8378. https://doi.org/10.1038/sj.onc.1207072
Denison, Stacy R. ; Wang, Fang ; Becker, Nicole A. ; Schüle, Birgitt ; Kock, Norman ; Phillips, Leslie A. ; Klein, Christine ; Smith, David I. / Alterations in the common fragile site gene Parkin in ovarian and other cancers. In: Oncogene. 2003 ; Vol. 22, No. 51. pp. 8370-8378.
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