Strauss B S
Department of Molecular Genetics and Cell Biology, The University of Chicago, Illinois 60637, USA.
Genetics. 1998 Apr;148(4):1619-26. doi: 10.1093/genetics/148.4.1619.
The presence of numerous chromosomal changes and point mutations in tumors is well established. At least some of these changes play a role in the development of the tumors. It has been suggested that the number of these genetic changes requires that tumorigenesis involves an increase in mutation rate. However, the presence of numerous changes can also be accounted for by efficient selection. What is required to settle the issue is some measure of nonselected mutations in tumors. In order to determine whether the tumor suppressor TP53 (coding for the protein p53) is hypermutable at some stage of carcinogenesis, the frequency of silent and multiple mutations in this gene has been examined. Silent mutations make up approximately 3% of the total recorded but constitute 9.5% of the mutations found in tumors with multiple mutations. Multiple closely linked mutations are also observed. Such multiple mutations suggest the operation of an error-prone replication process in a subclass of cells. The published data indicate that TP53 is hypermutable at some stage of tumor development. It is not yet clear whether TP53 is unique or whether other genes display a similar pattern of silent and multiple mutations.
肿瘤中存在大量染色体变化和点突变这一现象已得到充分证实。这些变化中至少有一些在肿瘤发展过程中发挥作用。有人提出，这些基因变化的数量表明肿瘤发生涉及突变率的增加。然而，大量变化的存在也可以用有效选择来解释。解决这个问题需要对肿瘤中的非选择性突变进行某种测量。为了确定肿瘤抑制基因TP53（编码p53蛋白）在致癌过程的某个阶段是否具有高突变性，已对该基因中沉默突变和多重突变的频率进行了研究。沉默突变约占记录总数的3%，但在具有多重突变的肿瘤中发现的突变中占9.5%。还观察到多个紧密连锁的突变。这种多重突变表明在一类细胞中存在易出错的复制过程。已发表的数据表明，TP53在肿瘤发展的某个阶段具有高突变性。目前尚不清楚TP53是否独特，或者其他基因是否表现出类似的沉默和多重突变模式。
