title: PDGFRA gain in low-grade diffuse gliomas.
abstract: Glioblastomas with a proneural expression signature are characterized by frequent IDH1 mutations (i.e. genetic hallmarks of secondary glioblastomas) and PDGFRA (platelet-derived growth factor receptor-α) amplification. Mutations in IDH1/2 are frequent and early genetic events in diffuse astrocytomas (World Health Organization grade II), precursor to secondary glioblastomas, but little is known about the role and timing of PDGFRA amplification in these tumors. We assessed PDGFRA gain in 342 low-grade diffuse gliomas by quantitative polymerase chain reaction. Gain in PDGFRA was detected in 27 (16.3%) of 166 diffuse astrocytomas, significantly more frequent than in oligodendrogliomas (3 [2.6%] of 115, p < 0.0001). Analyses using previously published data from our laboratory showed an inverse correlation between PDGFRA gain and IDH1/2 mutations (p = 0.018) or 1p/19q loss (p < 0.0001). The vast majority of diffuse astrocytomas showed IDH1/2 mutations and/or PDGFRA gain (154 [93%] of 166). Mean survival of diffuse astrocytoma patients with PDGFRA gain was 8.8 ± 1.6 years, similar to that with IDH1/2 mutations (7.8 ± 0.5 years) or TP53 mutations (7.6 ± 0.6 years) but significantly longer than those with MET gain (4.4 ± 0.7 years). Dual-color fluorescence in situ hybridization in 6 diffuse astrocytomas with PDGFRA/MET co-gain identified by quantitative polymerase chain reaction revealed that PDGFRA and MET were typically amplified in different tumor cell populations. Tumor cells with coamplification were also focally observed, suggesting intratumoral heterogeneity, even in diffuse astrocytomas.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Motomura
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brokinkel
authors.forename: Kathy
authors.initials: K
authors.lastname: Keyvani
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sure
authors.forename: Karsten
authors.initials: K
authors.lastname: Wrede
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Naosuke
authors.initials: N
authors.lastname: Nonoguchi
authors.forename: Daniela
authors.initials: D
authors.lastname: Pierscianek
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Anne
authors.initials: A
authors.lastname: Vital
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohgaki
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009837:Oligodendroglioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D015996:Survival Rate / Q000639:trends
chemical_list: D020796:Receptor, Platelet-Derived Growth Factor alpha