Learoyd D L, Twigg S M, Zedenius J V, Robinson B G
Molecular Genetics Unit, Kolling Institute of Medical Research, St. Leonards, NSW, Australia.
J Pediatr Endocrinol Metab. 1998 Mar-Apr;11(2):195-228. doi: 10.1515/jpem.1998.11.2.195.
The molecular genetics of endocrine tumours is an area of great interest, due to the heterogeneity of endocrine tumour types, the association of hormone over-production in some cases, and the wide variation in tumour behaviour. Genes implicated fall into functional categories such as oncogenes, in which mutations tend to cause activation, and tumour suppressor genes, in which mutations lead to loss of function. Oncogenes include the receptor tyrosine kinases such as RET, signal transduction proteins and other molecules such as cell cycle regulators and nuclear proteins. Tumour suppressor genes include cell cycle regulators such as p53 and other molecules such as the MEN 1 gene. Loss of heterozygosity studies help in the initial localisation of the latter. Endocrine tumours, as with other tumours, develop as a result of a combination of genetic events, and in the paediatric age group they often occur in the setting of familial cancer syndromes. In this review we analyse the main genetic lesions which have been described in endocrine tumours. There has been an explosion of knowledge in the last 5 years including the identification of the causative genes for MEN 2 and most recently for MEN 1. Characterisation of such genes also aids in the study of somatic mutations in sporadic versions of the same tumour types as occur in the familial syndromes. Identification of a genetic predisposition to a certain tumour has management implications that are still to be clarified in most cases, although in the case of MEN 2 the guidelines for prophylactic thyroidectomy are generally well accepted.
内分泌肿瘤的分子遗传学是一个备受关注的领域，这是由于内分泌肿瘤类型的异质性、某些情况下激素过度分泌的关联性以及肿瘤行为的广泛差异。涉及的基因可分为功能类别，如癌基因（其中的突变往往导致激活）和肿瘤抑制基因（其中的突变导致功能丧失）。癌基因包括受体酪氨酸激酶，如RET、信号转导蛋白以及其他分子，如细胞周期调节因子和核蛋白。肿瘤抑制基因包括细胞周期调节因子，如p53以及其他分子，如MEN 1基因。杂合性缺失研究有助于后者的初步定位。与其他肿瘤一样，内分泌肿瘤是由多种遗传事件共同作用而发生的，在儿童年龄组中，它们常发生于家族性癌症综合征的背景下。在本综述中，我们分析了内分泌肿瘤中已被描述的主要遗传病变。在过去5年里，相关知识呈爆发式增长，包括确定了MEN 2以及最近MEN 1的致病基因。对这些基因的特征描述也有助于研究与家族性综合征中相同肿瘤类型的散发性病例中的体细胞突变。确定对某种肿瘤的遗传易感性具有管理意义，在大多数情况下仍有待阐明，尽管就MEN 2而言，预防性甲状腺切除术的指导原则已普遍被接受。
