PARP1 expression in pediatric central nervous system tumors

Pediatr Blood Cancer. 2009 Dec 15;53(7):1227-30. doi: 10.1002/pbc.22141.

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.

Procedure: 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).

Conclusion: These findings indicate that PARP1 is expressed in high-grade pediatric CNS tumors, implicating PARP1 inhibition as a potential therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Central Nervous System Neoplasms / genetics
  • Central Nervous System Neoplasms / metabolism*
  • Central Nervous System Neoplasms / pathology
  • Child
  • Choroid Plexus Neoplasms / genetics
  • Choroid Plexus Neoplasms / metabolism
  • Choroid Plexus Neoplasms / pathology
  • DNA Damage
  • DNA Repair
  • Drug Delivery Systems
  • Gene Expression Profiling*
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neuroectodermal Tumors, Primitive / genetics
  • Neuroectodermal Tumors, Primitive / metabolism
  • Neuroectodermal Tumors, Primitive / pathology
  • Oligonucleotide Array Sequence Analysis
  • Papilloma / genetics
  • Papilloma / metabolism
  • Papilloma / pathology
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / biosynthesis*
  • Poly(ADP-ribose) Polymerases / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Single-Blind Method

Substances

  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases