Jones P A, Rideout W M, Shen J C, Spruck C H, Tsai Y C
Kenneth Norris Jr. Comprehensive Cancer Center, USC School of Medicine, Los Angeles 90033.
Bioessays. 1992 Jan;14(1):33-6. doi: 10.1002/bies.950140107.
The fifth base in human DNA, 5-methylcytosine, is inherently mutagenic. This has led to marked changes in the distribution of the CpG methyl acceptor site and an 80% depletion in its frequency of occurrence in vertebrate DNA. The coding regions of many genes contain CpGs which are methylated in sperm and serve as hot spots for mutation in human genetic diseases. Fully 30-40% of all human germline point mutations are thought to be methylation induced even though the CpG dinucleotide is under-represented and efficient cellular repair systems exist. Importantly, tumor suppressor genes such as p53 also contain methylated CpGs and these serve as hot spots for mutations in some, but not all, human cancers. Comparison of the spectrum of mutations present in this gene in different human cancers allows for predictions to be made on the molecular mechanisms of tumorigenesis.
人类DNA中的第五种碱基5-甲基胞嘧啶具有内在的诱变作用。这导致了CpG甲基受体位点分布的显著变化，其在脊椎动物DNA中的出现频率减少了80%。许多基因的编码区域含有在精子中甲基化的CpG，它们是人类遗传疾病中突变的热点。尽管CpG二核苷酸的含量较低且存在有效的细胞修复系统，但所有人类种系点突变中仍有30%-40%被认为是由甲基化诱导的。重要的是，诸如p53等肿瘤抑制基因也含有甲基化的CpG，它们在一些（但不是所有）人类癌症中是突变热点。比较该基因在不同人类癌症中存在的突变谱有助于对肿瘤发生的分子机制进行预测。
