A Study of Platelet-Derived Growth Factor A and Its Ligand among Patients with Glioblastoma and Astrocytoma in Imam Khomeini Hospital Complex, Tehran

Abstract

10.30699/jambs.31.146.230 Background&Objective: The platelet-derived growth factor receptor (PDGFR) signaling pathway has a vital function as a regulator of glioma development. PDGFRA alterations have been observed in a variety of cancers and have been important clinical targets for tyrosine kinase inhibitors like Imatinib. The aim of this study was to evaluate the role of PDGFRA and PDGFA in the pathogenesis of GBM and to determine whether the constitutive activation of PDGFRA is driven by gene mutations or protein expression. Materials&Methods: PDGFRA-activating gene mutations (exons 12, 18) were assessed in a subset of 75 samples, of which 65 were GBM and 10 were pilocytic astrocytoma, using PCR followed by direct sequencing. PDGFA expression was evaluated by immunohistochemistry in a series of 20 cases including 15 cases of glioblastoma multiforme and 5 cases of pilocytic astrocytoma. Results: No PDGFRA-activating mutations were found by Sanger sequencing. In addition, this study found polymorphism in PDGFRA exon 12, c.1701A> G, which was a silent mutation. Immunohistochemical analysis showed elevated PDGFA expression in 25% (5 out of 20) of glioma cases. PDGFA expression was not detected in any pilocytic astrocytoma; however, 33.33% (5 out of 15) of GBM samples showed increased PDGFA expression. Conclusion: Consistent with previous studies, the findings of the present study underline the importance of PDGFA and PDGFRA alterations as a possible potential predictive biomarker and a therapeutic target in GBM. Further research is needed to better understand the underlying genetic mechanisms driving abnormal PDGFRA activity in gliomas.