Wynford-Thomas D
Department of Pathology, University of Wales College of Medicine, Cardiff, UK.
Horm Res. 1997;47(4-6):145-57. doi: 10.1159/000185458.
Tumours of the thyroid follicular cell are proving to be one of the most informative models for "dissecting' the molecular genetics of multi-stage human tumorigenesis. Early thyroid tumour development is closely correlated with mutation of five alternative genes, ras, ret, trk, gsp and the TSH receptor, associated with different tumour phenotypes, providing an excellent example of genotype/phenotype correlation. For two of these genes, ras and ret, there is also direct experimental evidence from gene transfer studies that they are sufficient to initiate tumorigenesis, one of very few situations where such proof of causality has been obtained for a human tumour. Much less is known of the molecular basis of malignant transformation in thyroid. However, the rare, further progression to undifferentiated (anaplastic) cancer provides a particularly clear-cut illustration of the role of the tumour-suppressor gene p53 in human cancer. Furthermore, in vitro data suggest the intriguing possibility that the anaplastic phenotype results from a combination of p53 mutation together with a spontaneous switch in differentiation programme, i.e. co-operation between a genetic and an epigenetic event.
甲状腺滤泡细胞肿瘤正成为“剖析”多阶段人类肿瘤发生分子遗传学的最具信息价值的模型之一。甲状腺肿瘤的早期发展与五个替代基因（ras、ret、trk、gsp和促甲状腺激素受体）的突变密切相关，这些基因与不同的肿瘤表型相关，为基因型/表型相关性提供了一个极好的例子。对于其中两个基因，ras和ret，基因转移研究也有直接的实验证据表明它们足以引发肿瘤发生，这是在人类肿瘤中获得这种因果关系证据的极少数情况之一。关于甲状腺恶性转化的分子基础，人们了解得要少得多。然而，罕见的进一步发展为未分化（间变性）癌的情况特别清楚地说明了肿瘤抑制基因p53在人类癌症中的作用。此外，体外数据表明了一种有趣的可能性，即间变性表型是由p53突变与分化程序的自发转变共同导致的，也就是说，是一个遗传事件和一个表观遗传事件之间的协同作用。
