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 apo...

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Bibliographic Details
Published in:European journal of cancer (1990) 2001-11, Vol.37 (17), p.2217-2221
Main Authors: Catchpoole, D.R, Lock, R.B
Format: Article
Language:English
Subjects:
Apoptosis
Base Sequence
Biological and medical sciences
Caspase 9
Caspase-9 (CASP9)
Caspases - genetics
Cell Transformation, Neoplastic - genetics
Child
DNA, Complementary - genetics
DNA, Neoplasm - genetics
Gene Silencing
Genes, Tumor Suppressor
Humans
Medical sciences
Molecular Sequence Data
Mutation
Neuroblastoma
Neuroblastoma - genetics
Neurology
Polymorphism
Polymorphism, Single Nucleotide
Tumorigenesis
Tumors of the nervous system. Phacomatoses
Tumour suppressor gene
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Summary: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.
ISSN:0959-8049
1879-0852
DOI:10.1016/S0959-8049(01)00273-8