The potential tumour suppressor role for caspase-9 (CASP9) in the childhood malignancy, neuroblastoma
The potential tumour suppressor role for caspase-9 (CASP9) in the childhood malignancy, neuroblastoma
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DOI：
10.1016/s0959-8049(01)00273-8
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发表时间：
2001-11-01
影响因子：
8.4
通讯作者：
Lock, RB
中科院分区：
文献类型：
--
作者：
Catchpoole, DR;Lock, RB
神经母细胞瘤是一种源自神经嵴的神经外胚层细胞的儿童胚胎肿瘤，其临床侵袭性被认为是由细胞增殖、分化和凋亡之间的竞争性相互作用决定的。 Caspase-9 是细胞凋亡机制中的核心效应酶。最近对 caspase-9 (CASP9) 敲除小鼠的研究表明，神经系统发育早期阶段细胞凋亡减少导致大脑存在主要缺陷。我们的假设是，通过基因突变沉默 CASP9 可能会促进神经母细胞瘤的发生。在这里，我们报告了筛选神经母细胞瘤肿瘤 CASP9 沉默突变的结果。对从代表神经母细胞瘤临床病理疾病全范围的 22 个神经母细胞瘤肿瘤中分离的 RNA 制备的 cDNA 进行了测序。在所有神经母细胞瘤中均检测到单核苷酸变化，但发现并不代表沉默突变，而是序列多态性。这些多态性与患者的临床病理阶段或疾病或预测的临床结果无关。因此，CASP9 的沉默突变不太可能是神经母细胞瘤肿瘤发生的原因。 (C) 2001 Elsevier Science Ltd. 保留所有权利。
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 or disease or the predicted clinical outcomes of the patients. Silencing mutations of CASP9 are therefore unlikely to be causal to neuroblastoma tumorigenesis. (C) 2001 Elsevier Science Ltd. All rights reserved.