Martuza R L
Clin Neurosurg. 1983;31:417-40. doi: 10.1093/neurosurgery/31.cn_suppl_1.417.
This review provides a framework for the neurosurgeon in understanding the increasingly important role of genetics in the study of nervous system tumors. The three tumors discussed (retinoblastoma, meningioma, and neurofibroma) are neither the most common nor the most clinically devastating tumors faced by neurosurgeons. Rather, the studies on these tumors are presented because of the important lessons each provides. Studies of retinoblastoma demonstrate the ability of a gene which is recessive at the cellular level to require a second mutation for tumorigenesis and therein to appear as a dominantly inherited disorder at the level of the organism. This "multi-hit" theory could easily be applied to other nervous system tumors which have both sporadic solitary tumors and familial multiple tumors. In this group we should include acoustic neuromas, meningiomas, gliomas, neurofibromas, paragangliomas (glomus and carotid body tumors), and the pituitary tumors (and others) associated with the multiple endocrine neoplasia syndromes. The limits of this review do not allow a separate discussion of the neurosurgical aspect of these lesions; for this, the reader is referred elsewhere (18, 19). Meningiomas are discussed because it appears that two separate lines of inquiry may eventually be related at a cellular level. These directions of study are the demonstration that a common karyotypic abnormality (monosomy 22) is associated with a female preponderance of meningiomas and the demonstration of sex hormone binding in meningiomas. Future studies should be aimed at showing an in vitro biologic response of these tumors to exogenously added hormones or to their blocking agents. Moreover, one would hope that this response would correlate with a specific chromosomal abnormality. It is possible that some portion of the DNA which has been deleted or altered in these tumors plays an essential role in the regulation of the sex steroid regulatory system. If this segment of the genome could be identified and studied in the meningioma, the findings could be important not only in the treatment of patients with this tumor but also in the treatment of tumors of other hormonally modulated tissues such as breast and uterus. Finally, neurofibromatosis was chosen as the most common of the phakomatoses and as one which can offer significant insights into many areas of neuro-oncology. The NF gene occurs in at least two forms (VRNF, BANF), and it can be associated with virtually all of the tumors known to neurosurgeons--gliomas, neurofibromas, schwannomas, and meningiomas.(ABSTRACT TRUNCATED AT 400 WORDS)
本综述为神经外科医生提供了一个框架，以理解遗传学在神经系统肿瘤研究中日益重要的作用。所讨论的三种肿瘤（视网膜母细胞瘤、脑膜瘤和神经纤维瘤）既不是神经外科医生所面临的最常见肿瘤，也不是临床上最具破坏性的肿瘤。相反，之所以介绍这些肿瘤的研究，是因为它们各自都提供了重要的经验教训。视网膜母细胞瘤的研究表明，一个在细胞水平上呈隐性的基因，在肿瘤发生时需要第二次突变，从而在生物体水平上表现为显性遗传疾病。这种“多打击”理论很容易应用于其他神经系统肿瘤，这些肿瘤既有散发性孤立肿瘤，也有家族性多发性肿瘤。在这一组中，我们应包括听神经瘤、脑膜瘤、胶质瘤、神经纤维瘤、副神经节瘤（球瘤和颈动脉体瘤）以及与多发性内分泌肿瘤综合征相关的垂体肿瘤（及其他肿瘤）。本综述的篇幅限制不允许单独讨论这些病变的神经外科方面；为此，读者可参考其他文献（18, 19）。讨论脑膜瘤是因为似乎两条不同的研究线索最终可能在细胞水平上相关联。这些研究方向包括：证明一种常见的核型异常（22号染色体单体）与脑膜瘤女性居多有关，以及证明脑膜瘤中有性激素结合现象。未来的研究应旨在显示这些肿瘤对外源性添加的激素或其阻断剂的体外生物学反应。此外，人们希望这种反应能与特定的染色体异常相关。有可能在这些肿瘤中缺失或改变的部分DNA在性类固醇调节系统的调控中起重要作用。如果能在脑膜瘤中鉴定并研究这一基因组片段，其发现不仅对该肿瘤患者的治疗很重要，而且对其他受激素调节的组织如乳腺和子宫的肿瘤治疗也很重要。最后，神经纤维瘤病被选为最常见的错构瘤，并且它能为神经肿瘤学的许多领域提供重要见解。NF基因至少以两种形式存在（VRNF、BANF），它几乎可与神经外科医生所知的所有肿瘤相关联——胶质瘤、神经纤维瘤、神经鞘瘤和脑膜瘤。（摘要截选至400字）
