title: PDGFRA amplification is common in pediatric and adult high-grade astrocytomas and identifies a poor prognostic group in IDH1 mutant glioblastoma.
abstract: High-grade astrocytomas (HGAs), corresponding to World Health Organization grades III (anaplastic astrocytoma) and IV (glioblastoma; GBM), are biologically aggressive, and their molecular classification is increasingly relevant to clinical management. PDGFRA amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence in situ hybridization (FISH), the most sensitive technique for detecting PDGFRA copy number gains, we determined PDGFRA amplification status in 123 pediatric and 263 adult HGAs. A range of PDGFRA FISH patterns were identified and cases were scored as non-amplified (normal and polysomy) or amplified (low-level and high-level). PDGFRA amplification was frequent in pediatric (29.3%) and adult (20.9%) tumors. Amplification was not prognostic in pediatric HGAs. In adult tumors diagnosed initially as GBM, the presence of combined PDGFRA amplification and isocitrate dehydrogenase 1 (IDH1)(R132H) mutation was a significant independent prognostic factor (P = 0.01). In HGAs, PDGFRA amplification is common and can manifest as high-level and focal or low-level amplifications. Our data indicate that the latter is more prevalent than previously reported with copy number averaging techniques. To our knowledge, this is the largest survey of PDGFRA status in adult and pediatric HGAs and suggests PDGFRA amplification increases with grade and is associated with a less favorable prognosis in IDH1 mutant de novo GBMs.
authors: Department of Pathology, University of California San Francisco, San Francisco, CA, USA. joanna.phillips@ucsf.edu
authors: Joanna J
authors: JJ
authors: Phillips
authors: Derick
authors: D
authors: Aranda
authors: David W
authors: DW
authors: Ellison
authors: Alexander R
authors: AR
authors: Judkins
authors: Sidney E
authors: SE
authors: Croul
authors: Daniel J
authors: DJ
authors: Brat
authors: Keith L
authors: KL
authors: Ligon
authors: Craig
authors: C
authors: Horbinski
authors: Sriram
authors: S
authors: Venneti
authors: Gelareh
authors: G
authors: Zadeh
authors: Mariarita
authors: M
authors: Santi
authors: Shengmei
authors: S
authors: Zhou
authors: Christina L
authors: CL
authors: Appin
authors: Stefano
authors: S
authors: Sioletic
authors: Lisa M
authors: LM
authors: Sullivan
authors: Maria
authors: M
authors: Martinez-Lage
authors: Aaron E
authors: AE
authors: Robinson
authors: William H
authors: WH
authors: Yong
authors: Timothy
authors: T
authors: Cloughesy
authors: Albert
authors: A
authors: Lai
authors: Heidi S
authors: HS
authors: Phillips
authors: Roxanne
authors: R
authors: Marshall
authors: Sabine
authors: S
authors: Mueller
authors: Daphne A
authors: DA
authors: Haas-Kogan
authors: Annette M
authors: AM
authors: Molinaro
authors: Arie
authors: A
authors: Perry
mesh_terms: D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D012737:Sex Factors; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: FISH; IDH1; PDGFRA; astrocytoma; isocitrate dehydrogenase 1; prognosis