Prevalence, clinico-pathological value, and cooccurrence 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, in-cluding 167 grade II, 168 grade III, and 284 grade IV gliomas, with use of BAC-aCGH and validated our find-ings by quantitative polymerase chain reaction (PCR). We studied PDGFRA expression using reverse-transcrip-tion 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; pres-ence of KDR-PDGFRA fusion gene; and PDGFRA trun-cation. PDGFRAwas amplified and gained in 5.2 % and 1.9 % of samples, respectively. In addition PDGFRAwas point-mutated, rearranged, and truncated in 2.9%, 0%, and 0.7 % of cases, respectively. PDGFRA point muta-tions 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 am-plification 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 prognos-tic biomarker in anaplastic gliomas