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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

KIAA1549: BRAF Gene Fusion and FGFR1 Hotspot Mutations Are Prognostic Factors in Pilocytic Astrocytomas

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Autor(es):
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Becker, Aline Paixao [1, 2] ; Scapulatempo-Neto, Cristovam [3] ; Carloni, Adriana C. [1] ; Paulino, Alessandra [1] ; Sheren, Jamie [4] ; Aisner, Dara L. [4] ; Musselwhite, Evelyn ; Clara, Carlos [5] ; Machado, Helio R. ; Oliveira, Ricardo S. [6] ; Neder, Luciano [2] ; Varella-Garcia, Marileila [7] ; Reis, Rui M. [8, 9, 1]
Número total de Autores: 13
Afiliação do(s) autor(es):
[1] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Pathol & Forens Med, Fac Med Ribeirao Preto, Sao Paulo - Brazil
[3] Barretos Canc Hosp, Dept Pathol, Sao Paulo - Brazil
[4] Univ Colorado, Ctr Canc, Aurora, CO - USA
[5] Barretos Canc Hosp, Dept Neurosurg, Sao Paulo - Brazil
[6] Univ Sao Paulo, Dept Surg, Fac Med Ribeirao Preto, Sao Paulo - Brazil
[7] Univ Colorado, Sch Med, Aurora, CO - USA
[8] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga - Portugal
[9] ICVS 3Bs PT Govt Associate Lab, Braga - Portugal
Número total de Afiliações: 9
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY; v. 74, n. 7, p. 743-754, JUL 2015.
Citações Web of Science: 30
Resumo

Up to 20% of patients with pilocytic astrocytoma (PA) experience a poor outcome. BRAF alterations and Fibroblast growth factor receptor 1 (FGFR1) point mutations are key molecular alterations in Pas, but their clinical implications are not established. We aimed to determine the frequency and prognostic role of these alterations in a cohort of 69 patients with PAs. We assessed KIAA1549:BRAF fusion by fluorescence in situ hybridization and BRAF (exon 15) mutations by capillary sequencing. In addition, FGFR1 expression was analyzed using immunohistochemistry, and this was compared with gene amplification and hotspot mutations (exons 12 and 14) assessed by fluorescence in situ hybridization and capillary sequencing. KIAA1549:BRAF fusion was identified in almost 60% of cases. Two tumors harbored mutated BRAF. Despite high FGFR1 expression overall, no cases had FGFR1 amplifications. Three cases harbored a FGFR1 p.K656E point mutation. No correlation was observed between BRAF and FGFR1 alterations. The cases were predominantly pediatric (87%), and no statistical differences were observed in molecular alterations-related patient ages. In summary, we confirmed the high frequency of KIAA1549:BRAF fusion in PAs and its association with a better outcome. Oncogenic mutations of FGFR1, although rare, occurred in a subset of patients with worse outcome. These molecular alterations may constitute alternative targets for novel clinical approaches, when radical surgical resection is unachievable. (AU)

Processo FAPESP: 12/19590-0 - Perfil mutacional de linhagens primárias de glioblastomas
Beneficiário:Rui Manuel Vieira Reis
Linha de fomento: Auxílio à Pesquisa - Regular