PDGFRA Amplification is Common in Pediatric and Adult High‐Grade Astrocytomas and Identifies a Poor Prognostic Group in IDH1 Mutant Glioblastoma. (18th March 2013)

• Record Type: Journal Article
• Authors: Phillips, Joanna J.; Aranda, Derick; Ellison, David W.; Judkins, Alexander R.; Croul, Sidney E.; Brat, Daniel J.; Ligon, Keith L.; Horbinski, Craig; Venneti, Sriram; Zadeh, Gelareh; Santi, Mariarita; Zhou, Shengmei; Appin, Christina L.; Sioletic, Stefano; Sullivan, Lisa M.; Martinez‐Lage, Maria; Robinson, Aaron E.; Yong, William H.; Cloughesy, Timothy; Lai, Albert; Phillips, Heidi S.; Marshall, Roxanne; Mueller, Sabine; Haas‐Kogan, Daphne A.; Molinaro, Annette M.; Perry, Arie
• Is Part Of: Brain pathology. Volume 23:Number 5(2013:Sep.)
• Page Start: 565
• Page End: 573
• Publication Date: 2013-03-18
• Subjects: Nervous system -- Diseases -- Periodicals; Brain -- Diseases -- Periodicals; Neurology -- Periodicals; Brain Diseases -- Periodicals; Cerveau -- Maladies -- Périodiques; Système nerveux -- Maladies -- Périodiques; Neurologie -- Périodiques; 616.805
• DOI: 10.1111/bpa.12043
• Languages: English
• ISSNs: 1015-6305

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>High‐grade astrocytomas (HGAs), corresponding to World Health Organization grades III (anaplastic astrocytoma) and IV (glioblastoma; GBM), are biologically aggressive, and their molecular classification is increasingly relevant to clinical management. <italic>PDGFRA</italic> amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence <italic>in situ</italic> hybridization (FISH), the most sensitive technique for detecting <italic>PDGFRA</italic> copy number gains, we determined <italic>PDGFRA</italic> amplification status in 123 pediatric and 263 adult HGAs. A range of <italic>PDGFRA</italic> FISH patterns were identified and cases were scored as non‐amplified (normal and polysomy) or amplified (low‐level and high‐level). <italic>PDGFRA</italic> amplification was frequent in pediatric (29.3%) and adult (20.9%) tumors. Amplification was not prognostic in pediatric HGAs. In adult tumors diagnosed initially as GBM, the presence of combined <italic>PDGFRA</italic> amplification and isocitrate dehydrogenase 1 (IDH1)<sup>R132H</sup> mutation was a significant independent prognostic factor (<italic>P</italic> = 0.01). In HGAs, <italic>PDGFRA</italic> amplification is common and can manifest as high‐level and focal or low‐level amplifications. Our data indicate that the latter is more prevalent than previously reported with copy number averaging techniques. To our knowledge, this is the largest survey of <italic>PDGFRA</italic> status in adult and pediatric HGAs and suggests <italic>PDGFRA</italic> amplification increases with grade and is associated with a less favorable prognosis in IDH1 mutant de novo GBMs.</p> </abstract>