Trojanowski J Q, Fung K M, Rorke L B, Tohyama T, Yachnis A T, Lee V M
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia.
Mol Chem Neuropathol. 1994 Feb-Apr;21(2-3):219-39. doi: 10.1007/BF02815352.
Recent advances in understanding the basic biology of the neoplastic cells that populate childhood primitive neuroectodermal tumors (PNET) of the central nervous system (CNS) underline several unique properties of these common pediatric brain neoplasms. For example, studies of posterior fossa cerebellar medulloblastomas (MB), a prototypical group of brain tumors that comprise the largest class of PNET, suggest that the molecular phenotype of subpopulations of neoplastic cells in MB partially recapitulates stages in the acquisition of the neuronal phenotype by normal developing human CNS progenitor cells. However, as reviewed here, it appears that the neoplastic cells in MB exhibit one or more molecular defects in the sequence of normal maturational events that enable CNS progenitor cells to exit the cell cycle, become committed to the neuronal lineage, and undergo terminal differentiation into fully mature, permanently postmitotic CNS neurons. Indeed, since PNET emerge almost exclusively in early childhood, the induction of PNET may result from genetic lesions that arise in developing CNS progenitor cells thereby preventing these neural precursors from executing normal programs of lineage commitment and differentiation in the CNS. Clarification of how lineage commitment and maturation in PNET comprised of neuron-like tumor cells deviate from normal CNS development may clarify how oncogenes and tumor suppressor genes exert their effects in a cell type specific manner at different stages in the normal maturation of CNS cells. Recently, a number of potentially effective in vitro and in vivo model systems of PNET have been developed. Since these model systems could facilitate efforts to elucidate mechanisms of neoplastic transformation and tumor progression in the CNS, we review the potential utility of several recently described in vitro (e.g., MB cell lines) and in vivo (e.g., transgenic mice) experimental systems as models of authentic childhood CNS neoplasms.
在理解构成中枢神经系统（CNS）儿童原始神经外胚层肿瘤（PNET）的肿瘤细胞基本生物学方面的最新进展，突显了这些常见儿科脑肿瘤的几个独特特性。例如，对后颅窝小脑髓母细胞瘤（MB）的研究表明，MB是一组典型的脑肿瘤，也是PNET中最大的类别，其肿瘤细胞亚群的分子表型部分重现了正常发育的人类CNS祖细胞获得神经元表型的阶段。然而，如本文所述，MB中的肿瘤细胞似乎在正常成熟事件序列中表现出一个或多个分子缺陷，这些事件使CNS祖细胞能够退出细胞周期、定向于神经元谱系并经历终末分化成为完全成熟的、永久停止有丝分裂的CNS神经元。事实上，由于PNET几乎只出现在儿童早期，PNET的诱发可能源于发育中的CNS祖细胞中出现的基因损伤，从而阻止这些神经前体细胞在CNS中执行正常的谱系定向和分化程序。阐明由神经元样肿瘤细胞组成的PNET中的谱系定向和成熟如何偏离正常CNS发育，可能会阐明癌基因和肿瘤抑制基因如何在CNS细胞正常成熟的不同阶段以细胞类型特异性方式发挥作用。最近，已经开发了一些潜在有效的PNET体外和体内模型系统。由于这些模型系统有助于阐明CNS中肿瘤转化和肿瘤进展的机制，我们综述了几种最近描述的体外（如MB细胞系）和体内（如转基因小鼠）实验系统作为真实儿童CNS肿瘤模型的潜在用途。
