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Evidence that instability within the FRA3B region extends four megabases

Oncogene volume 21, pages 8713–8722 (2002)Cite this article

Abstract

FRA3B is the most frequently expressed common fragile site localized within human chromosomal band 3p14.2, which is frequently deleted in many different cancers, including cervical cancer. Previous reports indicate aphidicolin-induced FRA3B instability occurs over ∼500 kb which is spanned by the 1.5 Mb fragile histidine triad (FHIT) gene. Recently an HPV16 cervical tumor integration, 2 Mb centromeric to the published FRA3B region, has been identified. FISH-based analysis with a BAC spanning the integration has demonstrated this integration occurs within the FRA3B region of instability. These data suggest that the unstable FRA3B region is much larger than previously reported. FISH-based analysis of aphidicolin-induced metaphase chromosomes allowed for a complete characterization of instability associated with FRA3B. This analysis indicates that fragility extends for 4 Mb. Within this region are a total of five genes, including FHIT. FRA3B gene expression analysis on a panel of cervical tumor-derived cell lines revealed that three of the five genes within FRA3B were aberrantly regulated. A similar analysis of genes outside of FRA3B indicated that the surrounding genes were not aberrantly expressed. These data provide additional support that regions of instability associated with CFSs and the genes contained within them, may play an important role in cancer development.

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Abbreviations

BAC:

bacterial artificial chromosome

CFS:

common fragile site

FISH:

fluorescence in situ hybridization

FS:

fragile site

HPV:

human papillomavirus

Mb:

megabase pairs

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Acknowledgements

Supported by NIH Grant CA 48031 and Department of Defense Grant DAMD 17-99-1-9504 to DI Smith.

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Authors and Affiliations

  1. Department of Experimental Pathology, Mayo Foundation, Rochester, 55905, Minnesota, MN, USA

    Nicole A Becker, Stacy R Denison, Leslie A Phillips & David I Smith

  2. Departments of Biochemistry and Molecular Biology, Mayo Foundation, Rochester, 55905, Minnesota, MN, USA

    Erik C Thorland

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  1. Nicole A Becker
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Correspondence to David I Smith.

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Becker, N., Thorland, E., Denison, S. et al. Evidence that instability within the FRA3B region extends four megabases. Oncogene 21, 8713–8722 (2002). https://doi.org/10.1038/sj.onc.1205950

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