Molecular Profiling of a Rare Rosette-Forming Glioneuronal Tumor Arising in the Spinal Cord

Autor(es):Mostrar menos -

Bidinotto, Lucas Tadeu ^{[1, 2]} ; Scapulatempo-Neto, Cristovam ^{[3, 1]} ; Mackay, Alan ^[4] ; de Almeida, Gisele Caravina ^[3] ; Scheithauer, Bernd Walter ^[5] ; Berardinelli, Gustavo Noriz ^[1] ; Torrieri, Raul ^[1] ; Clara, Carlos Afonso ^[6] ; Feltrin, Leonir Terezinha ^[7] ; Viana-Pereira, Marta ^{[8, 9]} ; Varella-Garcia, Marileila ^[10] ; Jones, Chris ^[4] ; Reis, Rui Manuel ^{[8, 1, 9]}

Afiliação do(s) autor(es)

^[1] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, SP - Brazil

^[2] Dr Paulo Prata FACISB, Barretos Sch Hlth Sci, Barretos, SP - Brazil

^[3] Barretos Canc Hosp, Dept Pathol, Barretos, SP - Brazil

^[4] Inst Canc Res, Div Mol Pathol & Canc Therapeut, London SW3 6JB, Surrey - England

^[5] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN - USA

^[6] Barretos Canc Hosp, Dept Neurosurg, Barretos, SP - Brazil

^[7] Barretos Canc Hosp, Dept Radiol, Barretos, SP - Brazil

^[8] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga - Portugal

^[9] 3Bs PT Govt Associate Lab, Braga - Portugal

^[10] Univ Colorado Anschutz Med Campus, Med Oncol Dept Med, Aurora, CO - USA

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 9 SEP 15 2015.
• Citações Web of Science: 12

Resumo

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 genesMLL2, 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. (AU)

• Processo FAPESP: 11/08523-7 - Perfil de alterações cromossômicas em tumores cerebrais (meduloblastomas e gliomas): impacto na identificação de novas vias tumorigênicas
• Beneficiário: Lucas Tadeu Bidinotto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/08287-4 - Perfil de alterações cromossômicas em gliomas
• Beneficiário: Lucas Tadeu Bidinotto
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 12/19590-0 - Perfil mutacional de linhagens primárias de glioblastomas
• Beneficiário: Rui Manuel Vieira Reis
• Modalidade de apoio: Auxílio à Pesquisa - Regular