Predominant occurrence of somatic mutations of the NF2 gene in meningiomas and schwannomas
P. Mérel
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, Paris, France
Search for more papers by this authorK. Hoang-Xuan
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, Paris, France
Service de Neurologic, CHU Pitié-Salpetrière, Paris, France
Search for more papers by this authorM. Sanson
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, Paris, France
Service de Neurologic, CHU Pitié-Salpetrière, Paris, France
Search for more papers by this authorA. Moreau-Aubry
Laboratoire de Génétique des Espécés, INSERM U21, I, Paris, France
Search for more papers by this authorE. K. Bijlsma
Institute of Human Genetics, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorC. Lazaro
Department de Genética Molecular, Institu de Recerca Oncologica, Hospital Duran i Reynals Autovia de Castelldefels, Barcelona, Spain
Search for more papers by this authorJ. P. Moisan
Laboratoire de Génétique des Espécés, INSERM U21, I, Paris, France
Search for more papers by this authorF. Resche
Service de Neurochirurgie, CHU Nantes, Nastes, France
Search for more papers by this authorI. Nishisho
Division of Clinical Genetics, Bromedical Research Center, Osaka University Medical School, Osaka, Japan
Search for more papers by this authorX. Estivill
Department de Genética Molecular, Institu de Recerca Oncologica, Hospital Duran i Reynals Autovia de Castelldefels, Barcelona, Spain
Search for more papers by this authorJ. Y. Delattre
Service de Neurologic, CHU Pitié-Salpetrière, Paris, France
Search for more papers by this authorM. Poisson
Service de Neurologic, CHU Pitié-Salpetrière, Paris, France
Search for more papers by this authorC. Theillet
Institut de Génétique Moléculaire, CNRS UMR 9942, Montpellier, France
Search for more papers by this authorT. Hulsebos
Institute of Human Genetics, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorO. Delattre
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, Paris, France
Search for more papers by this authorCorresponding Author
G. Thomas
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, Paris, France
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, 26 rue d'Ulm, 75231 Paris Cedex 05, FranceSearch for more papers by this authorP. Mérel
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, Paris, France
Search for more papers by this authorK. Hoang-Xuan
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, Paris, France
Service de Neurologic, CHU Pitié-Salpetrière, Paris, France
Search for more papers by this authorM. Sanson
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, Paris, France
Service de Neurologic, CHU Pitié-Salpetrière, Paris, France
Search for more papers by this authorA. Moreau-Aubry
Laboratoire de Génétique des Espécés, INSERM U21, I, Paris, France
Search for more papers by this authorE. K. Bijlsma
Institute of Human Genetics, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorC. Lazaro
Department de Genética Molecular, Institu de Recerca Oncologica, Hospital Duran i Reynals Autovia de Castelldefels, Barcelona, Spain
Search for more papers by this authorJ. P. Moisan
Laboratoire de Génétique des Espécés, INSERM U21, I, Paris, France
Search for more papers by this authorF. Resche
Service de Neurochirurgie, CHU Nantes, Nastes, France
Search for more papers by this authorI. Nishisho
Division of Clinical Genetics, Bromedical Research Center, Osaka University Medical School, Osaka, Japan
Search for more papers by this authorX. Estivill
Department de Genética Molecular, Institu de Recerca Oncologica, Hospital Duran i Reynals Autovia de Castelldefels, Barcelona, Spain
Search for more papers by this authorJ. Y. Delattre
Service de Neurologic, CHU Pitié-Salpetrière, Paris, France
Search for more papers by this authorM. Poisson
Service de Neurologic, CHU Pitié-Salpetrière, Paris, France
Search for more papers by this authorC. Theillet
Institut de Génétique Moléculaire, CNRS UMR 9942, Montpellier, France
Search for more papers by this authorT. Hulsebos
Institute of Human Genetics, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorO. Delattre
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, Paris, France
Search for more papers by this authorCorresponding Author
G. Thomas
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, Paris, France
Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, 26 rue d'Ulm, 75231 Paris Cedex 05, FranceSearch for more papers by this authorAbstract
The NF2 gene is a putative tumor-suppressor gene that, when it is altered in the germline, causes neurofibromatosis type 2, a tumor-susceptibility disease that mainly predisposes to schwannomas and meningiomas. The recent isolation of the NF2 gene on chromosome 22 allows the identification of somatic mutations in human tumors. We have searched for mutations of the NF2 gene in 331 primary human tumors using a screening method based on denaturing gradient gel electrophoresis, which allows the detection of mutations in 95% of the coding sequence. Mutations were observed in 17 of 57 meningiomas and in 30 of 89 schwannomas. No mutations were observed for 17 ependymomas, 70 gliomas, 23 primary melanomas, 24 pheochromocytomas, 15 neuroblastomas, 6 medulloblastomas, 15 colon cancers, and 15 breast cancers. All meningiomas and one-half of the schwannomas with identified NF2 mutations demonstrated chromosome 22 allelic losses. We conclude that the involvement of the NF2 gene in human tumorigenesis may be restricted to schwannomas and meningiomas, where it is frequently inactivated by a two-hit process. © 1995 Wiley-Liss, Inc.
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