Characterization of the common fragile site FRA9E and its potential role in ovarian cancer. Oncogene 2003 Jan 30;22(4):590-601
Date
01/30/2003Pubmed ID
12555072DOI
10.1038/sj.onc.1206171Scopus ID
2-s2.0-0037473048 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
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 9 Mb, 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.
Author List
Callahan G, Denison SR, Phillips LA, Shridhar V, Smith DIAuthor
Gwen Lomberk PhD Adjunct Professor in the Institute for Health and Humanity department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Base SequenceChromosome Fragile Sites
Chromosome Fragility
DNA
Female
Gene Expression Profiling
Humans
In Situ Hybridization, Fluorescence
Loss of Heterozygosity
Ovarian Neoplasms
Reverse Transcriptase Polymerase Chain Reaction
