The potential tumour suppressor role for caspase-9 (CASP9) in the childhood malignancy, neuroblastoma.
The clinical aggressiveness of neuroblastoma, a childhood embryonal tumour of neuroectodermal cells derived from the neural crest, is considered to be dictated by the competitive interactions between cell proliferation, differentiation and apoptosis. Caspase-9 is a central effector enzyme in the apoptotic mechanism. Recent studies with caspase-9 (CASP9) knockout mice indicate a primary defect in the brain caused by decreased apoptosis during the early stages of nervous system development. It is our hypothesis that silencing of CASP9 through genetic mutations may promote neuroblastoma tumorigenesis. Here, we report the outcome of screening neuroblastoma tumours for silencing mutations in CASP9. cDNA prepared from RNA isolated from 22 neuroblastoma tumours representing the full range of neuroblastoma clinicopathological disease stages was sequenced. Single nucleotide changes were detected in all neuroblastoma tumours, but were found not to represent silencing mutations, but rather sequence polymorphisms. These polymorphisms did not associate with the clinicopathological stages of disease or the predicted clinical outcomes of the patients. Silencing mutations of CASP9 are therefore unlikely to be causal to neuroblastoma tumorigenesis.
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Children's Cancer Institute Australia for Medical Research, PO Box 81, Randwick, NSW 2031, Australia. danielc@chw.edu.au
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D001483:Base Sequence; D053453:Caspase 9; D020169:Caspases / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002648:Child; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D018076:DNA, Complementary; D004273:DNA, Neoplasm; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases