文章：

神经肿瘤的分子和遗传基础

The Molecular and Genetic Basis of Neurological Tumours

原文发布日期：2002-08-01

DOI: 10.1038/nrc866

类型: Review Article

开放获取: 否

要点：

1. Tumours of neuroectodermal origin (neurological tumours) include all neoplasms of the central nervous system (CNS) and peripheral nervous system (PNS). The classification of neurological tumours is based on their predominant cell type(s) as they relate to normal cell types that are present in the CNS and PNS.
2. Glial cells retain proliferative properties throughout life. So, most neurological tumours are of glial-lineage origin. In the CNS, gliomas include astrocytomas, oligodendrogliomas and oligoastrocytomas. In the PNS, neurofibromas and schwannomas are common tumours.
3. Genetic pathways that are involved in the initiation and progression of astrocytomas have been identified. In secondary glioblastoma multiforme (GBM), loss of p53 and activation of the growth-factor–receptor-tyrosine-kinase signalling pathway initiates tumour formation, whereas disruption of the retinoblastoma (RB) pathway contributes to the progression of tumour development.
4. Similar genetic pathways are disrupted in primary GBM, although through different mechanisms. The rapid growth nature of the primary GBM indicates that this type of malignancy might arise from the transformation of adult neural stem cells, which either are present in the brain or can be de-differentiated from astrocytes in response to oncogenic mutations.
5. Dermal neurofibromas are thought to be derived from a component of mature Schwann cells, whereas plexiform neurofibromas are believed to arise from an embryonic Schwann-cell lineage. Most malignant peripheral-nerve-sheath tumours are derived from neurofibromas — particularly plexiform neurofibromas.
6. Disruption of neurofibromatosis type 1 (NF1) in the Schwann-cell lineage initiates neurofibroma formation. In the setting of plexiform neurofibroma, the heterozygous state of tumour environment is important for tumour formation. The disruption of the p53 pathway is involved in the malignant progression of neurofibroma.

要点翻译：

1. 神经外胚层起源的肿瘤（神经系统肿瘤）包括所有中枢神经系统（CNS）和周围神经系统（PNS）的肿瘤。神经系统肿瘤的分类基于其主要细胞类型，这些细胞类型与CNS和PNS中存在的正常细胞类型相关。
2. 胶质细胞在整个生命周期中保持增殖特性，因此大多数神经系统肿瘤源自胶质细胞谱系。在中枢神经系统中，胶质瘤包括星形细胞瘤、少突胶质细胞瘤和少突星形细胞瘤。在周围神经系统中，神经纤维瘤和神经鞘瘤是常见肿瘤。
3. 目前已明确星形细胞瘤发生和进展涉及的遗传通路。在继发性多形性胶质母细胞瘤（GBM）中，p53缺失和生长因子受体酪氨酸激酶信号通路的激活会启动肿瘤形成，而视网膜母细胞瘤（RB）通路失调则促进肿瘤发展进程。
4. 原发性GBM虽通过不同机制发生，但存在类似的遗传通路失调。原发性GBM的快速生长特性表明，这类恶性肿瘤可能源于成人神经干细胞的转化——这些干细胞或存在于大脑中，或可因致癌突变从星形胶质细胞去分化而来。
5. 皮肤神经纤维瘤被认为源自成熟雪旺细胞的组成部分，而从状神经纤维瘤则被认为起源于胚胎雪旺细胞谱系。大多数恶性周围神经鞘瘤源自神经纤维瘤——特别是从状神经纤维瘤。
6. 雪旺细胞谱系中1型神经纤维瘤病（NF1）基因的失调会启动神经纤维瘤的形成。在从状神经纤维瘤中，肿瘤环境的杂合状态对肿瘤形成至关重要。p53通路的失调参与神经纤维瘤的恶性进展过程。

英文摘要：

There are no effective therapies for many tumours of the nervous system. This is, in part, a consequence of their location within relatively inaccessible tissues. It is also likely, however, that the unique characteristics of the cells that give rise to these tumours create a set of conditions that facilitate tumour development. Here, we consider recent advances in molecular genetics, the development of mouse models and developmental neurobiology as they relate to tumours of neuroectodermal origin. It is likely that these advances will provide insight into underlying mechanisms and provide a rational framework for the development of effective interventions.

摘要翻译： 

许多神经系统肿瘤尚无有效治疗手段，部分原因在于它们位于相对难以触及的组织中。然而，更可能的是，这些肿瘤起源细胞的独特特性创造了一组有利于肿瘤发展的条件。在此，我们结合分子遗传学的最新进展、小鼠模型的建立以及发育神经生物学，探讨它们与神经外胚层源性肿瘤的关系。这些进展有望揭示其潜在机制，并为制定有效干预措施提供理论框架。

原文链接：

The Molecular and Genetic Basis of Neurological Tumours