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Characterization of a conserved aphidicolin-sensitive common fragile site at human 4q22 and mouse 6C1: possible association with an inherited disease and cancer

Oncogene volume 23, pages 6872–6880 (2004)Cite this article

Abstract

Fragile sites are classified as common or rare depending on their occurrence in the populations. While rare sites are mainly associated with inherited diseases, common sites have been involved in somatic rearrangements found in the chromosomes of cancer cells. Here we study a mouse locus containing the ionotropic glutamate receptor delta 2 (grid2) gene in which spontaneous chromosome rearrangements occur frequently, giving rise to mutant animals in inbred populations. We identify and clone common fragile sites overlapping the mouse grid2 gene and its human ortholog GRID2, lying respectively at bands 6C1 and 4q22 in a 7-Mb-long region of synteny. These results show a third example of orthologous common sites conserved at the molecular level, and reveal an unexpected link between an inherited disease and an aphidicolin-sensitive region. Recurrent deletions of subregions of band 4q22 have been previously described in human hepatocellular carcinomas. This 15-Mb-long region appears precisely centered on the site described here, which strongly suggests that it also plays a specific role in hepatic carcinogenesis.

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Abbreviations

AP:

aphidicolin

BAC:

bacterial artificial chromosome

BCG:

break, constriction or gap

CFS:

common fragile site

FCS:

fetal calf serum

FISH:

fluorescent in situ hybridization

Grid2:

glutamate ionotropic delta 2 receptor

HCC:

hepatocellular carcinomas

MGD:

mouse genome database (http://www.informatics.jacks.org)

RFS:

rare fragile site

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Acknowledgements

We thank A Lalouette for providing the BAC 316M9, J-L Guenet and B Dutrillaux for interesting discussions and G Buttin for critical reading of the manuscript and helpful discussions. This work was supported in part by the Association pour la Recherche sur le Cancer (ARC), the Ligue Nationale Française contre le Cancer (Comité d'Ile-de-France), and the Fondation pour la Recherche Médicale. LR is a Fellow of the French government (MENRT).

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  1. Instabilité du génome et cancer, FRE2584-CNRS, Institut Curie, 26 rue d'Ulm, Paris Cédex 05, 75248, France

    Lorène Rozier, Eliane El-Achkar, Françoise Apiou & Michelle Debatisse

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Correspondence to Michelle Debatisse.

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Rozier, L., El-Achkar, E., Apiou, F. et al. Characterization of a conserved aphidicolin-sensitive common fragile site at human 4q22 and mouse 6C1: possible association with an inherited disease and cancer. Oncogene 23, 6872–6880 (2004). https://doi.org/10.1038/sj.onc.1207809

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