Pritchard-Jones K
Institute of Cancer Research/Royal Marsden NHS Trust, Sutton, Surrey, UK.
Br Med Bull. 1996 Oct;52(4):704-23. doi: 10.1093/oxfordjournals.bmb.a011578.
In the last 5 years, there has been a tremendous increase in understanding of the molecular genetics of several childhood cancers. The genes for more than 10 cancer predisposition syndromes are now cloned and the molecular basis of their functioning is being analysed. The classical model of inherited cancer predisposition being due to mutation of tumour suppressor genes is being expanded to include genes involved in DNA processing and weakly dominant oncogenes. The chromosomal translocation characteristic of specific types of sporadic tumours are yielding to the molecular knife, with the isolation of many of the genes disrupted in both leukaemias and solid tumours. Common structural motifs are seen among the proteins which are brought together by translocation to produce novel fusion proteins. Detection of translocations in solid tumours has been made simpler by the introduction of molecular techniques which do not rely on karyotyping.
在过去五年中，人们对几种儿童癌症的分子遗传学的理解有了极大的提高。目前，超过10种癌症易感性综合征的基因已被克隆，其功能的分子基础正在被分析。经典的遗传性癌症易感性模型认为是由于肿瘤抑制基因的突变，现在这个模型正在扩展，将涉及DNA加工的基因和弱显性癌基因也包括在内。特定类型的散发性肿瘤所特有的染色体易位，正受到分子手术刀的剖析，许多在白血病和实体瘤中被破坏的基因已被分离出来。通过易位聚集在一起产生新型融合蛋白的蛋白质之间，可见共同的结构基序。不依赖于核型分析的分子技术的引入，使实体瘤中易位的检测变得更简单。
