Exomic Sequencing of Four Rare Central Nervous System Tumor Types

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Bettegowda, Chetan ^{[1, 2]} ; Agrawal, Nishant ^{[2, 3]} ; Jiao, Yuchen ^[2] ; Wang, Yuxuan ^[2] ; Wood, Laura D. ^[4] ; Rodriguez, Fausto J. ^[4] ; Hruban, Ralph H. ^[4] ; Gallia, Gary L. ^[1] ; Binder, Zev A. ^[1] ; Riggins, Callen J. ^[1] ; Salmasi, Vafi ^[5] ; Riggins, Gregory J. ^[1] ; Reitman, Zachary J. ^[6] ; Rasheed, Ahmed ^[6] ; Keir, Stephen ^[6] ; Shinjo, Sueli ^[7] ; Marie, Suely ^[7] ; McLendon, Roger ^[6] ; Jallo, George ^[1] ; Vogelstein, Bert ^[2] ; Bigner, Darell ^[6] ; Yan, Hai ^[6] ; Kinzler, Kenneth W. ^[2] ; Papadopoulos, Nickolas ^[2]

Afiliação do(s) autor(es)

^[1] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 - USA

^[2] Johns Hopkins Univ, Sch Med, Ludwig Ctr Canc Genet, Baltimore, MD - USA

^[3] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 - USA

^[4] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 - USA

^[5] Cleveland Clin Hosp, Dept Anesthesiol, Cleveland, OH - USA

^[6] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC - USA

^[7] Univ Sao Paulo, Dept Pathol, Sch Med, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ONCOTARGET; v. 4, n. 4, p. 572-583, APR 2013.
• Citações Web of Science: 41

Resumo

A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric glioblastomas (PGBM), 8 intracranial ependymomas (IEP) and 8 spinal cord ependymomas (SCEP). Analysis of the mutational spectra revealed that the predominant single base pair substitution was a C: G>T: A transition in each of the four tumor types. Our data confirm the critical roles of several known driver genes within CNS neoplasms, including TP53 and ATRX in PGBM, and NF2 in SCEPs. Additionally, we show that activating BRAF mutations play a central role in both low and high grade glial tumors. Furthermore, alterations in genes coding for members of the mammalian target of rapamycin (mTOR) pathway were observed in 33% of PXA. Our study supports the hypothesis that pathologically similar tumors arising in different age groups and from different compartments may represent distinct disease processes with varied genetic composition. (AU)

• Processo FAPESP: 04/12133-6 - Procura de marcadores moleculares relacionados ao diagnóstico e prognóstico de tumores do sistema nervoso central
• Beneficiário: Suely Kazue Nagahashi Marie
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 01/12898-4 - Genoma clínico
• Beneficiário: Suely Kazue Nagahashi Marie
• Modalidade de apoio: Auxílio à Pesquisa - Programa GENOMA