Amplification of the PDGFRA, KIT and KDR genes in glioblastoma: a population-based study

Abstract

The aim of this study was to establish the frequency of amplification of tyrosine kinase receptor genes PDGFRA, KIT and KDR (VEGFR2) at 4q12 in glioblastomas at a population level, and to assess whether such alterations have any clinical impact. Screening of 390 glioblastomas from a population-based study by differential PCR revealed amplification of the PDGFRA, KIT and KDR genes in 33 (8.5%), 17 (4.4%) and 13 (3.3%) glioblastomas, respectively. None of these alterations was prognostic for overall survival. Patients with glioblastoma showing KIT amplification were significantly younger than those with glioblastoma showing no amplification (51.7 ± 21.7 years vs. 59.3 ± 13.1 years; P=0.0231). Twelve glioblastomas showed concurrent amplification of the PDGFRA, KIT and KDR genes, whereas 18 glioblastomas showed PDGFRA amplification only. A significant inverse association was observed between KIT amplification and EGFR amplification (P=0.0260), whereas a borderline positive association was found between KIT amplification and TP53 mutation (P=0.0579). No significant difference was observed in the frequency of amplification of these genes in primary and secondary glioblastomas or in glioblastomas with and without IDH1 mutations, suggesting that amplification of PDGFRA, KIT and KDR may be implicated in the pathogenesis of a small fraction of both subtypes of glioblastoma.

Distinct genetic alterations in pediatric glioblastomas

“…Nobusawa et al [15] found the amplification of tyrosine kinase receptor gene PDGFRA in 8.3 % of GBs, and reported no significant difference between primary and secondary aGBs or between GBs with and without IDH1 mutations. Moreover, PDGFRA amplification was found more frequently in irradiation-induced HGGs and less frequently in both aGBs and pGBs, and it did not apparently affect patient survival [15].…”

“…Moreover, PDGFRA amplification was found more frequently in irradiation-induced HGGs and less frequently in both aGBs and pGBs, and it did not apparently affect patient survival [15]. Nobusawa et al [15] concluded that PDGFA may be implicated in the pathogenesis of a small fraction of GBs.…”

“…The mean age of the patients was 8.8 (range, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] years, and the male to female ratio was nearly 2.3:1. Diagnoses were based on histological and immunohistochemical features according to the 2007 WHO classification system and were reviewed by three pathologists (PSH, BSJ, and KSH).…”

“…In pediatric HGGs, the reported frequencies of EGFR gene amplification and EGFR vIII mutations and deletions are low (11, 0, and 17 %, respectively) [12]. PDGFR α polypeptide (PDGFRA) gene amplification was detected in only a small subset of aGBs and 12 % of pGBs [13][14][15].…”

Regulation of Angiogenesis in Human Cancer via Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2)

“…A population based study conducted by Nobusawa et al of 390 glioblastomas using differential PCR demonstrated amplification of PDGFRA, KIT and VEGFR-2 genes in 33 (8.5%), 17 (4.4%) and 13 (3.3%) of glioblastomas respectively. None of these alterations were prognostic for overall survival (Nobusawa et al 2011). …”