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 journalArticlepeer-review

164 Scopus citations


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
Issue number51
StatePublished - Nov 13 2003


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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


Dive into the research topics of 'Alterations in the common fragile site gene Parkin in ovarian and other cancers'. Together they form a unique fingerprint.

Cite this