Characterization of the common fragile site FRA9E and its potential role in ovarian cancer

Gwen Callahan, Stacy R. Denison, Leslie A. Phillips, Viji Shridhar, David I. Smith

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Common fragile sites (CFSs) are regions of profound genomic instability that have been hypothesized to play a role in cancer. The major aim of this study was to locate a fragile region associated with ovarian cancer. Differential display (DD)-PCR analysis comparing normal ovarian epithelial cultures and ovarian cancer cell lines identified pregnancy-associated plasma protein-A (PAPPA) because of its frequent loss of expression (LOE) in ovarian cancer cell lines. PAPPA is localized to human chromosome 9q32-33.1, a region associated with significant loss of heterozygosity (LOH) in ovarian tumors (> 50%) and in close proximity to the FRA9E CFS. FISH analysis determined that PAPPA was contained within the distal end of FRA9E. Characterization of FRA9E determined that aphidicolin-induced instability extended over 9Mb, identifying FRA9E as the largest CFS characterized to date. Comprehensive LOH analysis revealed several distinct peaks of LOH within FRA9E. Semiquantitative RT-PCR analysis of 16 genes contained within FRA9E indicated that genes showing LOE in ovarian tumors coincided with regions of high LOH. PAPPA displayed the most significant loss (72%). This study provides evidence to suggest that instability within FRA9E may play an important role in the development of ovarian cancer and lends further support for the hypothesis that CFSs may be causally related to cancer.

Original languageEnglish (US)
Pages (from-to)590-601
Number of pages12
JournalOncogene
Volume22
Issue number4
DOIs
StatePublished - Jan 30 2003

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Pregnancy-Associated Plasma Protein-A
Loss of Heterozygosity
Ovarian Neoplasms
Neoplasms
Aphidicolin
Cell Line
Polymerase Chain Reaction
Genomic Instability
Human Chromosomes
Genes
Ovarian epithelial cancer

Keywords

  • Chromosomal deletions
  • Common fragile sites
  • FRA9E
  • Ovarian cancer
  • PAPPA

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Callahan, G., Denison, S. R., Phillips, L. A., Shridhar, V., & Smith, D. I. (2003). Characterization of the common fragile site FRA9E and its potential role in ovarian cancer. Oncogene, 22(4), 590-601. https://doi.org/10.1038/sj.onc.1206171

Characterization of the common fragile site FRA9E and its potential role in ovarian cancer. / Callahan, Gwen; Denison, Stacy R.; Phillips, Leslie A.; Shridhar, Viji; Smith, David I.

In: Oncogene, Vol. 22, No. 4, 30.01.2003, p. 590-601.

Research output: Contribution to journalArticle

Callahan, G, Denison, SR, Phillips, LA, Shridhar, V & Smith, DI 2003, 'Characterization of the common fragile site FRA9E and its potential role in ovarian cancer', Oncogene, vol. 22, no. 4, pp. 590-601. https://doi.org/10.1038/sj.onc.1206171
Callahan, Gwen ; Denison, Stacy R. ; Phillips, Leslie A. ; Shridhar, Viji ; Smith, David I. / Characterization of the common fragile site FRA9E and its potential role in ovarian cancer. In: Oncogene. 2003 ; Vol. 22, No. 4. pp. 590-601.
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