Prevalence, clinico-pathological value, and co-occurrence of PDGFRA abnormalities in diffuse gliomas.
PDGFRA is a critical gene in glioma biology. Similar to EGFR, PDGFRA has been shown to be overexpressed, amplified, mutated, or truncated in gliomas, particularly glioblastomas. In addition, PDGFRA has been recently shown to be rearranged in glioblastoma. However, the frequency, cooccurrence, and clinical value of PDGFRA abnormalities in diffuse gliomas remain unclear. We investigated PDGFRA abnormalities and their clinical impact on 619 primary diffuse gliomas, including 167 grade II, 168 grade III, and 284 grade IV gliomas, with use of BAC-aCGH and validated our findings by quantitative polymerase chain reaction (PCR). We studied PDGFRA expression using reverse-transcription quantitative PCR in 84 gliomas and 12 non-tumor samples. In 138 samples, we also screened PDGFRA point mutations in exons 5, 7, 8, 9, 10, 11, and 23; presence of KDR-PDGFRA fusion gene; and PDGFRA truncation. PDGFRA was amplified and gained in 5.2% and 1.9% of samples, respectively. In addition PDGFRA was point-mutated, rearranged, and truncated in 2.9%, 0%, and 0.7% of cases, respectively. PDGFRA point mutations were observed exclusively in grade IV gliomas and in 12.5% of PDGFRA-amplified tumors. High-level PDGFRA amplification was associated with PDGFRA overexpression, high malignancy grade, and older patient age. Of interest, high-level PDGFRA amplification has an independent negative prognostic value for progression-free survival and overall survival among patients with grade III tumors. PDGFRA is altered through various genetic mechanisms in a subset of high-grade gliomas in patients who might be ideal candidates for PDGFRA inhibitor treatment, and PDGFRA gene amplification could be used as a prognostic biomarker in anaplastic gliomas.
CRICM, INSERM UMRS 975/CNRS UMR 7225/UPMC, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Neurology2-Mazarin, Paris, France.
Agustí
A
Alentorn
Yannick
Y
Marie
Catherine
C
Carpentier
Blandine
B
Boisselier
Marine
M
Giry
Marianne
M
Labussière
Karima
K
Mokhtari
Khê
K
Hoang-Xuan
Marc
M
Sanson
Jean-Yves
JY
Delattre
Ahmed
A
Idbaih
D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020796:Receptor, Platelet-Derived Growth Factor alpha