title: Exomic sequencing of four rare central nervous system tumor types.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. cbetteg1@jhmi.edu
authors.forename: Chetan
authors.initials: C
authors.lastname: Bettegowda
authors.forename: Nishant
authors.initials: N
authors.lastname: Agrawal
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Jiao
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Laura D
authors.initials: LD
authors.lastname: Wood
authors.forename: Fausto J
authors.initials: FJ
authors.lastname: Rodriguez
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Gary L
authors.initials: GL
authors.lastname: Gallia
authors.forename: Zev A
authors.initials: ZA
authors.lastname: Binder
authors.forename: Callen J
authors.initials: CJ
authors.lastname: Riggins
authors.forename: Vafi
authors.initials: V
authors.lastname: Salmasi
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Reitman
authors.forename: Ahmed
authors.initials: A
authors.lastname: Rasheed
authors.forename: Stephen
authors.initials: S
authors.lastname: Keir
authors.forename: Sueli
authors.initials: S
authors.lastname: Shinjo
authors.forename: Suely
authors.initials: S
authors.lastname: Marie
authors.forename: Roger
authors.initials: R
authors.lastname: McLendon
authors.forename: George
authors.initials: G
authors.lastname: Jallo
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Darell
authors.initials: D
authors.lastname: Bigner
authors.forename: Hai
authors.initials: H
authors.lastname: Yan
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Nickolas
authors.initials: N
authors.lastname: Papadopoulos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics*; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004806:Ependymoma / Q000235:genetics*; D059472:Exome; D005260:Female; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D055815:Young Adult