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. (c) 2009 Wiley-Liss, Inc.
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. (c) 2009 Wiley-Liss, Inc.
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