Rice Jerry M
Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20057-1465, USA.
Toxicol Appl Pharmacol. 2004 Sep 1;199(2):175-91. doi: 10.1016/j.taap.2003.12.031.
Pediatric neurogenic tumors include primitive neuroectodermal tumors (PNETs), especially medulloblastoma; ependymomas and choroid plexus papillomas; astrocytomas; retinoblastoma; and sympathetic neuroblastoma. Meningiomas and nerve sheath tumors, although uncommon in childhood, are also significant because they can result from exposures of children to ionizing radiation. Specific chromosomal loci and specific genes are related to each of these tumor types. Virtually all these genes appear to act as tumor suppressor genes, which are inactivated in tumor cells by mutations or by chromosomal loss. In genetically engineered mice, some genes that are clearly associated with specific human tumors (e.g., RB1 in retinoblastoma and NF2 in meningiomas and schwannomas) have no such effect. Other genetic constructs in mice involving the genes p53, ptc1, and Nf1 have produced tumors remarkably similar to some of the human pediatric neoplasms. Some of these tumors become clinically apparent after only a few weeks, while the mice are still juveniles, especially when two or more tumor suppressor genes are inactivated in the same genetic construct. Conversely, at least one genetic pathway in rodents involving point mutation in the coding region of a transforming gene (neu in malignant schwannomas) does not appear to operate in any human tumors. The nervous system is markedly susceptible to experimental carcinogenesis during early life in rodents, dogs, primates, and other nonhuman species, and there is no obvious reason why this generalization should not also apply to humans. However, except for therapeutic ionizing radiation, no physical, chemical, or biological cause of human pediatric nervous system tumors is known. The failure of experimental transplacental carcinogenesis to mirror human pediatric experience more closely may reflect the need for multiple mutational events in target cells, and for experimental carcinogens that are capable of causing the full spectrum of mutations that occur in cancer-related genes in pediatric neurogenic tumors.
小儿神经源性肿瘤包括原始神经外胚层肿瘤（PNETs），尤其是髓母细胞瘤；室管膜瘤和脉络丛乳头状瘤；星形细胞瘤；视网膜母细胞瘤；以及交感神经母细胞瘤。脑膜瘤和神经鞘瘤虽然在儿童期不常见，但也很重要，因为它们可能是儿童接触电离辐射所致。特定的染色体位点和特定基因与这些肿瘤类型中的每一种都有关。几乎所有这些基因似乎都起肿瘤抑制基因的作用，它们在肿瘤细胞中因突变或染色体缺失而失活。在基因工程小鼠中，一些与特定人类肿瘤明显相关的基因（如视网膜母细胞瘤中的RB1基因以及脑膜瘤和神经鞘瘤中的NF2基因）并没有这样的作用。小鼠中涉及p53、ptc1和Nf1基因的其他基因构建体产生的肿瘤与一些人类小儿肿瘤非常相似。其中一些肿瘤在小鼠仍为幼年时，仅几周后就会在临床上显现出来，尤其是当同一基因构建体中有两个或更多肿瘤抑制基因失活时。相反，啮齿动物中至少有一条涉及转化基因（恶性神经鞘瘤中的neu基因）编码区点突变的遗传途径似乎在任何人类肿瘤中都不起作用。在啮齿动物、狗、灵长类动物和其他非人类物种的早期生命中，神经系统对实验性致癌作用非常敏感，而且没有明显理由认为这种普遍情况不适用于人类。然而，除了治疗性电离辐射外，尚无已知的人类小儿神经系统肿瘤的物理、化学或生物学病因。实验性经胎盘致癌作用未能更紧密地反映人类小儿的情况，这可能反映了靶细胞需要多个突变事件，以及需要能够导致小儿神经源性肿瘤中与癌症相关基因发生的全谱突变的实验性致癌物。
