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  • Oncogenomics
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Hemizygosity of Nf2 is associated with increased susceptibility to asbestos-induced peritoneal tumours

Oncogene volume 22, pages 3799–3805 (2003)Cite this article

Abstract

Biallelic NF2 gene inactivation is frequently found in human malignant mesothelioma. In order to assess whether NF2 hemizygosity may enhance susceptibility to asbestos fibres, we investigated the Nf2 status in mesothelioma developed in mice presenting a heterozygous mutation of the Nf2 gene (Nf2KO3/+), after intraperitoneal inoculation of crocidolite fibres. Asbestos-exposed Nf2KO3/+ mice developed tumoural ascites and mesothelioma at a higher frequency than their wild-type (WT) counterparts (P<0.05). Six out of seven mesothelioma cell lines established from neoplastic ascitic fluids of Nf2KO3/+ mice exhibited loss of the WT Nf2 allele and no neurofibromatosis type 2 protein expression was found in these cells. The results show the importance of the NF2 gene in mesothelial oncogenesis, the potential association of asbestos exposure and tumour suppressor gene inactivation, and suggest that NF2 gene mutation may be a susceptibility factor to asbestos.

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Acknowledgements

This work was supported by INSERM funds, and grants from the Ministère de l’Emploi et de la Solidarité No. 1D004C and Ministère de l’Environnement No. AC008B. C Lecomte is a fellow by the Ministère de la Recherche. We thank Laurinda Maia for helpful technical assistance and Catherine Vaslin for typewritting the manuscript.

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Authors and Affiliations

  1. INSERM EMI 99.09, Université Paris XII, Faculté de Médecine, 8 rue du Général Sarrail, Créteil, 94010, France

    Jocelyne Fleury-Feith, Céline Lecomte, Annie Renier, Mireille Matrat, Laurence Kheuang, Françoise Levy & Marie-Claude Jaurand

  2. Service d'Histologie, Biologie tumorale Hôpital Tenon, Rue de la Chine, Paris, 75020, France

    Jocelyne Fleury-Feith

  3. Service de Pathologies Professionnelles, Centre Hospitalier Intercommunal, Créteil, 94010, France

    Mireille Matrat

  4. INSERM U 434, Fondation Jean Dausset – CEPH, 27 rue Juliette Dodu,  Paris, 75010, France

    Vincent Abramowski & Marco Giovannini

  5. Laboratoire de Pathologie, ERM 220 INSERM, Université Paris VII, Hôpital Saint Louis, 1 av Claude Vellefaux, Paris, 75010, France

    Anne Janin

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  1. Jocelyne Fleury-Feith
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Correspondence to Marie-Claude Jaurand.

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Fleury-Feith, J., Lecomte, C., Renier, A. et al. Hemizygosity of Nf2 is associated with increased susceptibility to asbestos-induced peritoneal tumours. Oncogene 22, 3799–3805 (2003). https://doi.org/10.1038/sj.onc.1206593

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