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Identification of recurrent SMO and BRAF mutations in ameloblastomas.
Sweeney, Robert T; McClary, Andrew C; Myers, Benjamin R; Biscocho, Jewison; Neahring, Lila; Kwei, Kevin A; Qu, Kunbin; Gong, Xue; Ng, Tony; Jones, Carol D; Varma, Sushama; Odegaard, Justin I; Sugiyama, Toshihiro; Koyota, Souichi; Rubin, Brian P; Troxell, Megan L; Pelham, Robert J; Zehnder, James L; Beachy, Philip A; Pollack, Jonathan R; West, Robert B.
Afiliación
  • Sweeney RT; 1] Department of Pathology, Stanford University, Stanford, California, USA. [2].
  • McClary AC; 1] Department of Pathology, Stanford University, Stanford, California, USA. [2].
  • Myers BR; 1] Department of Biochemistry, Stanford University, Stanford, California, USA. [2] Department of Developmental Biology, Stanford University, Stanford, California, USA. [3] Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. [4] Howard Hughes Med
  • Biscocho J; 1] Department of Pathology, Stanford University, Stanford, California, USA. [2].
  • Neahring L; 1] Department of Biochemistry, Stanford University, Stanford, California, USA. [2] Department of Developmental Biology, Stanford University, Stanford, California, USA. [3] Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. [4] Howard Hughes Med
  • Kwei KA; 1] Genomic Health, Redwood City, California, USA. [2].
  • Qu K; Genomic Health, Redwood City, California, USA.
  • Gong X; Department of Pathology, Stanford University, Stanford, California, USA.
  • Ng T; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
  • Jones CD; Department of Pathology, Stanford University, Stanford, California, USA.
  • Varma S; Department of Pathology, Stanford University, Stanford, California, USA.
  • Odegaard JI; Department of Pathology, Stanford University, Stanford, California, USA.
  • Sugiyama T; Department of Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.
  • Koyota S; Department of Biochemistry, Akita University Graduate School of Medicine, Akita, Japan.
  • Rubin BP; Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio, USA.
  • Troxell ML; Department of Pathology, Oregon Health and Sciences University, Portland, Oregon, USA.
  • Pelham RJ; Genomic Health, Redwood City, California, USA.
  • Zehnder JL; Department of Pathology, Stanford University, Stanford, California, USA.
  • Beachy PA; 1] Department of Biochemistry, Stanford University, Stanford, California, USA. [2] Department of Developmental Biology, Stanford University, Stanford, California, USA. [3] Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA. [4] Howard Hughes Med
  • Pollack JR; Department of Pathology, Stanford University, Stanford, California, USA.
  • West RB; Department of Pathology, Stanford University, Stanford, California, USA.
Nat Genet ; 46(7): 722-5, 2014 Jul.
Article en En | MEDLINE | ID: mdl-24859340
ABSTRACT
Here we report the discovery of oncogenic mutations in the Hedgehog and mitogen-activated protein kinase (MAPK) pathways in over 80% of ameloblastomas, locally destructive odontogenic tumors of the jaw, by genomic analysis of archival material. Mutations in SMO (encoding Smoothened, SMO) are common in ameloblastomas of the maxilla, whereas BRAF mutations are predominant in tumors of the mandible. We show that a frequently occurring SMO alteration encoding p.Leu412Phe is an activating mutation and that its effect on Hedgehog-pathway activity can be inhibited by arsenic trioxide (ATO), an anti-leukemia drug approved by the US Food and Drug Administration (FDA) that is currently in clinical trials for its Hedgehog-inhibitory activity. In a similar manner, ameloblastoma cells harboring an activating BRAF mutation encoding p.Val600Glu are sensitive to the BRAF inhibitor vemurafenib. Our findings establish a new paradigm for the diagnostic classification and treatment of ameloblastomas.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ameloblastoma / Neoplasias Maxilomandibulares / Receptores Acoplados a Proteínas G / Proteínas Proto-Oncogénicas B-raf / Mutación Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2014 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ameloblastoma / Neoplasias Maxilomandibulares / Receptores Acoplados a Proteínas G / Proteínas Proto-Oncogénicas B-raf / Mutación Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2014 Tipo del documento: Article