title: PARP1 expression in pediatric central nervous system tumors.
abstract: BACKGROUND
  Despite advances in therapy, outcome in many high-grade pediatric central nervous system (CNS) tumors remains poor. The focus of neuro-oncology research has thus turned towards identifying novel therapeutic targets. Poly(ADP-ribose) polymerase-1 (PARP1) is a DNA repair protein that has been studied in a variety of malignancies and may interfere with therapy-induced DNA damage, however expression in pediatric CNS tumors is unknown.
  
  
  METHODS
  We evaluated PARP1 mRNA expression in 81 pediatric CNS tumors using microarray technology. Protein expression was examined by Western blot.
  
  
  RESULTS
  PARP1 mRNA is highly expressed in high-grade tumors (P < 0.0001). PARP1 mRNA expression was greater in high-grade glioma than pilocytic astrocytoma (P = 3.5 x 10(-5)) and in large cell medulloblastoma over classic medulloblastoma (P = 0.0053). PARP1 protein was also prominent in high-grade tumors (P = 0.022).
  
  
  CONCLUSIONS
  These findings indicate that PARP1 is expressed in high-grade pediatric CNS tumors, implicating PARP1 inhibition as a potential therapeutic target.
authors.affiliation: Department of Pediatrics, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA. valerie.barton@ucdenver.edu
authors.forename: Valerie N
authors.initials: VN
authors.lastname: Barton
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Donson
authors.forename: B K
authors.initials: BK
authors.lastname: Kleinschmidt-DeMasters
authors.forename: Lia
authors.initials: L
authors.lastname: Gore
authors.forename: Arthur K
authors.initials: AK
authors.lastname: Liu
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Foreman
mesh_terms: D016543:Central Nervous System Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002648:Child; D016545:Choroid Plexus Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage; D004260:DNA Repair; D016503:Drug Delivery Systems; D020869:Gene Expression Profiling; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010212:Papilloma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D016037:Single-Blind Method
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases