Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma

Isabelle Janoueix-Lerosey, Delphine Lequin, Laurence Brugières, Agnès Ribeiro, Loïc de Pontual, Valérie Combaret, Virginie Raynal, Alain Puisieux, Gudrun Schleiermacher, Gaëlle Pierron, Dominique Valteau-Couanet, Thierry Frebourg, Jean Michon, Stanislas Lyonnet, Jeanne Amiel and Olivier Delattre ()
Additional contact information
Isabelle Janoueix-Lerosey: Institut Curie, Centre de Recherche,
Delphine Lequin: Institut Curie, Centre de Recherche,
Laurence Brugières: Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France
Agnès Ribeiro: Institut Curie, Unité de Génétique Somatique
Loïc de Pontual: Université Paris Descartes, Faculté de Médecine et INSERM-U781, Hôpital Necker-Enfants Malades, 149, rue de Sèvres, 75743 Paris Cedex 15, France
Valérie Combaret: Centre Léon Bérard, FNCLCC, Laboratoire de Recherche Translationnelle
Virginie Raynal: Institut Curie, Centre de Recherche,
Alain Puisieux: Centre Léon Bérard, FNCLCC, Laboratoire de Recherche Translationnelle
Gudrun Schleiermacher: Institut Curie, Centre de Recherche,
Gaëlle Pierron: Institut Curie, Unité de Génétique Somatique
Dominique Valteau-Couanet: Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France
Thierry Frebourg: Service de Génétique, CHU de Rouen et Inserm U614, Faculté de Médecine et de Pharmacie
Jean Michon: Institut Curie
Stanislas Lyonnet: Université Paris Descartes, Faculté de Médecine et INSERM-U781, Hôpital Necker-Enfants Malades, 149, rue de Sèvres, 75743 Paris Cedex 15, France
Jeanne Amiel: Université Paris Descartes, Faculté de Médecine et INSERM-U781, Hôpital Necker-Enfants Malades, 149, rue de Sèvres, 75743 Paris Cedex 15, France
Olivier Delattre: Institut Curie, Centre de Recherche,

Nature, 2008, vol. 455, issue 7215, 967-970

Abstract: Neuroblastoma: a genetic link to ALK Neuroblastoma is the most common childhood cancer. There is a strong familial association and it was predicted over 30 years ago that there was a genetic element to the disease. Four groups now report the identification of mutations in the tyrosine kinase receptor ALK (anaplastic lymphoma kinase) in neuroblastoma patients. ALK acts as a neuroblastoma predisposition gene, and somatic point mutations occur in sporadic neuroblastoma cases. These mutations promote ALK's kinase activity and can transform cells and display tumorigenic activity in vivo. ALK inhibitors decrease neuroblastoma cell proliferation, so have potential as anticancer drugs.

Date: 2008
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DOI: 10.1038/nature07398

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