Molecular profiling of a rare rosette-forming glioneuronal tumor arising in the spinal cord

• Autor(a) principal: Bidinotto, Lucas Tadeu
• Data de Publicação: 2015
• Outros Autores: Scapulatempo-Neto, Cristovam, Mackay, Alan, de Almeida, Gisele Caravina, Scheithauer, Bernd Walter, Berardinelli, Gustavo Noriz, Torrieri, Raul, Clara, Carlos Afonso, Feltrin, Leonir Terezinha, Pereira, Marta Sofia Carvalho Ribeiro Viana, Varella-Garcia, Marileila, Jones, Chris, Reis, R. M.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/62214
• topic: Adult; Brain Neoplasms; Chromosome Deletion; Exome; Humans; Magnetic Resonance Imaging; Male; Spinal Cord; Ciências Médicas::Medicina Básica; Science & Technology

Rosette-forming glioneuronal tumor (RGNT) of the IV ventricle is a rare and recently recognized brain tumor entity. It is histologically composed by two distinct features: a glial component, resembling pilocytic astrocytoma, and a component forming neurocytic rosettes and/or perivascular rosettes. Herein, we describe a 33-year-old man with RGNT arising in the spinal cord. Following an immunohistochemistry validation, we further performed an extensive genomic analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology. We observed the loss of 1p and gain of 1q, as well as gain of the whole chromosomes 7, 9 and 16. Local amplifications in 9q34.2 and 19p13.3 (encompassing the gene SBNO2) were identified. Moreover, we observed focal gains/losses in several chromosomes. Additionally, on chromosome 7, we identified the presence of the KIAA1549:BRAF gene fusion, which was further validated by RT-PCR and FISH. Across all mutational analyses, we detected and validated the somatic mutations of the genes MLL2, CNNM3, PCDHGC4 and SCN1A. Our comprehensive molecular profiling of this RGNT suggests that MAPK pathway and methylome changes, driven by KIAA1549:BRAF fusion and MLL2 mutation, respectively, could be associated with the development of this rare tumor entity.