Tumor Development Program, NCI-Designated Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Neuropathol Appl Neurobiol. 2012 Jun;38(3):228-40. doi: 10.1111/j.1365-2990.2011.01235.x.
Medulloblastoma, the most common malignant paediatric brain tumour, is thought to arise from mutations in progenitors or stem cells in the cerebellum. Recent molecular analyses have highlighted the heterogeneity of these tumours, and demonstrated that they can be classified into at least four major subtypes that differ in terms of gene expression, genomic gains and losses, epidemiology and patient outcome. Along with analysis of human tumours, a variety of animal models of medulloblastoma have been developed using transgenic and knockout technology as well as somatic gene delivery. These models have provided valuable insight into the origins of the disease and the signalling pathways that control tumour growth. But the degree to which current models recapitulate the heterogeneity of the human disease remains unclear. Here we review the recent literature on the genomics of medulloblastoma and discuss the relationship of mouse models to the subtypes of the disease. Judicious use of existing models, and generation of additional models for poorly studied subtypes of medulloblastoma, will increase our understanding of tumour biology and allow evaluation of novel approaches to treatment of the disease.
髓母细胞瘤是最常见的小儿脑恶性肿瘤,其被认为起源于小脑的祖细胞或干细胞中的突变。最近的分子分析强调了这些肿瘤的异质性,并证明它们可以至少分为四个主要亚型,这些亚型在基因表达、基因组增益和缺失、流行病学和患者预后方面存在差异。除了对人类肿瘤的分析外,还使用转基因和基因敲除技术以及体基因传递开发了各种髓母细胞瘤动物模型。这些模型为疾病的起源和控制肿瘤生长的信号通路提供了有价值的见解。但是,目前的模型在多大程度上再现了人类疾病的异质性尚不清楚。在这里,我们回顾了髓母细胞瘤基因组学的最新文献,并讨论了小鼠模型与该疾病亚型的关系。明智地使用现有的模型,并为研究较少的髓母细胞瘤亚型生成额外的模型,将提高我们对肿瘤生物学的理解,并允许评估治疗该疾病的新方法。