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Genome instability in secondary solid tumors developing after radiotherapy of bilateral retinoblastoma

Oncogene volume 20, pages 8092–8099 (2001)Cite this article

Abstract

Genome alterations of seven secondary tumors (five osteosarcomas, one malignant peripheral sheath nerve tumor, one leiomyosarcoma) occurring in the field of irradiation of patients treated for bilateral retinoblastoma have been studied. These patients were predisposed to develop radiation-induced tumors because of the presence of a germ line mutation in the retinoblastoma gene (RB1). Tumor cells were characterized by a high chromosome instability whereas microsatellites and minisatellites were found to be stable. In all tumors, the normal RB1 allele was lost with the corresponding chromosome 13, whereas the germ line mutated allele was retained. The two alleles of TP53 were inactivated, one by deletion of the short arm of chromosome 17, the other by mutation. As compared with non-radiation-induced tumors, the observed panel of TP53 mutations was uncommon with sites not recurrently found otherwise and a high rate of deletions (3/7). In these predisposed patients, the loss of the single normal allele of RB1 is rather due to the radiation-induced chromosome instability than a direct effect of ionizing radiation.

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Acknowledgements

This research was supported by grants from COGEMA (PIC D14), EDF (RB 2001–26) the European Community (FIGH-CT-1999-00002) and the Institut Curie ‘Programme Incitatif et Coopératif Génotoxicologie'. S–H Lefèvre was a fellow of the Ministère de l'Eduation Nationale et de la Recherche.

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Authors and Affiliations

  1. Institut Curie – CNRS UMR 147, 26 rue d'Ulm 75248 Paris Cedex 05, France

    Sandrine-Hélène Lefèvre, Nicolas Vogt, Anne-Marie Dutrillaux, Bernard Dutrillaux & Bernard Malfoy

  2. Institut Curie, Service de Radiothérapie, 26 rue d'Ulm 75248 Paris Cedex 05, France

    Laurent Chauveinc

  3. Institut Curie, Service de Génétique Oncologique, 26 rue d'Ulm 75248 Paris Cedex 05, France

    Dominique Stoppa-Lyonnet

  4. Institut Curie, Service de Pédiatrie, 26 rue d'Ulm 75248 Paris Cedex 05, France

    François Doz

  5. Institut Curie, Service d'Ophtalmologie, 26 rue d'Ulm 75248 Paris Cedex 05, France

    Laurence Desjardins

  6. CEA, DSV DRR, 60 avenue du Général Leclerc 92265 Fontenay-aux-Roses, France

    Bernard Dutrillaux & Sylvie Chevillard

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  1. Sandrine-Hélène Lefèvre
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  2. Nicolas Vogt
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Correspondence to Bernard Malfoy.

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Lefèvre, SH., Vogt, N., Dutrillaux, AM. et al. Genome instability in secondary solid tumors developing after radiotherapy of bilateral retinoblastoma. Oncogene 20, 8092–8099 (2001). https://doi.org/10.1038/sj.onc.1205009

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