PMID- 23438035 OWN - NLM STAT- MEDLINE DCOM- 20140314 LR - 20220311 IS - 1750-3639 (Electronic) IS - 1015-6305 (Print) IS - 1015-6305 (Linking) VI - 23 IP - 5 DP - 2013 Sep TI - PDGFRA amplification is common in pediatric and adult high-grade astrocytomas and identifies a poor prognostic group in IDH1 mutant glioblastoma. PG - 565-73 LID - 10.1111/bpa.12043 [doi] AB - 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. PDGFRA amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence in situ hybridization (FISH), the most sensitive technique for detecting PDGFRA copy number gains, we determined PDGFRA amplification status in 123 pediatric and 263 adult HGAs. A range of PDGFRA FISH patterns were identified and cases were scored as non-amplified (normal and polysomy) or amplified (low-level and high-level). PDGFRA 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 PDGFRA amplification and isocitrate dehydrogenase 1 (IDH1)(R132H) mutation was a significant independent prognostic factor (P = 0.01). In HGAs, PDGFRA 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 PDGFRA status in adult and pediatric HGAs and suggests PDGFRA amplification increases with grade and is associated with a less favorable prognosis in IDH1 mutant de novo GBMs. CI - (c) 2013 International Society of Neuropathology. FAU - Phillips, Joanna J AU - Phillips JJ AD - Department of Pathology, University of California San Francisco, San Francisco, CA, USA. joanna.phillips@ucsf.edu FAU - Aranda, Derick AU - Aranda D FAU - Ellison, David W AU - Ellison DW FAU - Judkins, Alexander R AU - Judkins AR FAU - Croul, Sidney E AU - Croul SE FAU - Brat, Daniel J AU - Brat DJ FAU - Ligon, Keith L AU - Ligon KL FAU - Horbinski, Craig AU - Horbinski C FAU - Venneti, Sriram AU - Venneti S FAU - Zadeh, Gelareh AU - Zadeh G FAU - Santi, Mariarita AU - Santi M FAU - Zhou, Shengmei AU - Zhou S FAU - Appin, Christina L AU - Appin CL FAU - Sioletic, Stefano AU - Sioletic S FAU - Sullivan, Lisa M AU - Sullivan LM FAU - Martinez-Lage, Maria AU - Martinez-Lage M FAU - Robinson, Aaron E AU - Robinson AE FAU - Yong, William H AU - Yong WH FAU - Cloughesy, Timothy AU - Cloughesy T FAU - Lai, Albert AU - Lai A FAU - Phillips, Heidi S AU - Phillips HS FAU - Marshall, Roxanne AU - Marshall R FAU - Mueller, Sabine AU - Mueller S FAU - Haas-Kogan, Daphne A AU - Haas-Kogan DA FAU - Molinaro, Annette M AU - Molinaro AM FAU - Perry, Arie AU - Perry A LA - eng GR - K08 NS063456/NS/NINDS NIH HHS/United States GR - 1U01CA168878/CA/NCI NIH HHS/United States GR - U01 CA168878/CA/NCI NIH HHS/United States GR - P01 CA095616/CA/NCI NIH HHS/United States GR - P50 CA097257/CA/NCI NIH HHS/United States GR - P01CA095616/CA/NCI NIH HHS/United States GR - K08 CA155764/CA/NCI NIH HHS/United States GR - CA097257/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130318 PL - Switzerland TA - Brain Pathol JT - Brain pathology (Zurich, Switzerland) JID - 9216781 RN - EC 1.1.1.41 (Isocitrate Dehydrogenase) RN - EC 1.1.1.42. (IDH1 protein, human) RN - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha) SB - IM MH - Adolescent MH - Adult MH - Astrocytoma/*genetics MH - Brain Neoplasms/*genetics MH - Child MH - Child, Preschool MH - Cohort Studies MH - DNA Copy Number Variations/*genetics MH - Female MH - Glioblastoma/*genetics MH - Humans MH - Isocitrate Dehydrogenase/*genetics MH - Male MH - Middle Aged MH - Mutation/*genetics MH - Receptor, Platelet-Derived Growth Factor alpha/*genetics MH - Sex Factors MH - Statistics, Nonparametric MH - Young Adult PMC - PMC3715570 MID - NIHMS452642 OTO - NOTNLM OT - FISH OT - IDH1 OT - PDGFRA OT - astrocytoma OT - isocitrate dehydrogenase 1 OT - prognosis COIS- The authors declare they have no conflict of interest. EDAT- 2013/02/27 06:00 MHDA- 2014/03/15 06:00 PMCR- 2013/03/18 CRDT- 2013/02/27 06:00 PHST- 2012/10/24 00:00 [received] PHST- 2013/02/11 00:00 [accepted] PHST- 2013/02/27 06:00 [entrez] PHST- 2013/02/27 06:00 [pubmed] PHST- 2014/03/15 06:00 [medline] PHST- 2013/03/18 00:00 [pmc-release] AID - BPA12043 [pii] AID - 10.1111/bpa.12043 [doi] PST - ppublish SO - Brain Pathol. 2013 Sep;23(5):565-73. doi: 10.1111/bpa.12043. Epub 2013 Mar 18.