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| 12 December 2002, Volume 21, Number 57, Pages 8713-8722 |
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| Original Paper |
| Evidence that instability within the FRA3B region extends four megabases |
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| Nicole A Becker1, Erik C Thorland2, Stacy R Denison1, Leslie A Phillips1 and David I Smith1 |
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1Department of Experimental Pathology, Mayo Foundation, Rochester, Minnesota, MN 55905, USA
2Departments of Biochemistry and Molecular Biology, Mayo Foundation, Rochester, Minnesota, MN 55905, USA
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Correspondence to: D I Smith, Department of Experimental Pathology, Mayo Foundation, Hilton 800, 200 First Street S.W., Rochester, MN 55905, USA; E-mail: smith.david@mayo.edu |
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| 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. Oncogene (2002) 21, 8713-8722. doi:10.1038/sj.onc.1205950 |
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| Keywords |
| common fragile sites; FRA3B; human papillomavirus; cervical cancer; viral integration |
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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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| Received 10 April 2002; revised 31 July 2002; accepted 7 August 2002 |
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| 12 December 2002, Volume 21, Number 57, Pages 8713-8722 |
| Table of contents Previous Abstract Next Full text PDF |
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