Somatic microindels in human cancer: the insertions are highly error-prone and derive from nearby but not adjacent sense and antisense templates.
Somatic microindels in human cancer: the insertions are highly error-prone and derive from nearby but not adjacent sense and antisense templates.
复制标题
DOI：
10.1093/hmg/ddn190
复制
发表时间：
2008-09
影响因子：
3.5
通讯作者：
W. Scaringe;Kai Li;D. Gu;K. Gonzalez;Zhenbin Chen;K. Hill;S. Sommer
中科院分区：
文献类型：
--
作者：
W. Scaringe;Kai Li;D. Gu;K. Gonzalez;Zhenbin Chen;K. Hill;S. Sommer
利用Big Blue Laci转基因突变检测系统对正常小鼠组织中的体细胞微缺失(微插入微缺失)进行了研究。在这里，我们使用一种内源性和转录的基因，TP53基因来分析人类癌症中的微Indels。微调频率、1-2微调增等特征与正常小鼠组织中观察到的非转录LacI基因基本相似。目前较大的体细胞微缺失样本揭示了递归：缺失相同而共定位插入相似的突变。数据显示，插入的序列来自附近的序列，而不是相邻的序列，这与绝大多数纯微插入的滑移形成对比。微插入序列来自具有相似频率的正义链或反义链上的模板。每个碱基13%的插入过程的估计错误率是迄今为止报道的体内最大的，可能是免疫球蛋白基因的体细胞高度突变的例外。这些数据限制了微Indels的可能机制，并提出了这样一个问题：微Indels是否是由转录型聚合酶绕过大的DNA加合物形成的“伤疤”，例如本文提出的“泰山模型”。
Somatic microindels (microdeletions with microinsertions) have been studied in normal mouse tissues using the Big Blue lacI transgenic mutation detection system. Here we analyze microindels in human cancers using an endogenous and transcribed gene, the TP53 gene. Microindel frequency, the enhancement of 1-2 microindels and other features are generally similar to that observed in the non-transcribed lacI gene in normal mouse tissues. The current larger sample of somatic microindels reveals recurroids: mutations in which deletions are identical and the co-localized insertion is similar. The data reveal that the inserted sequences derive from nearby but not adjacent sequences in contrast to the slippage that characterizes the great majority of pure microinsertions. The microindel inserted sequences derive from a template on the sense or antisense strand with similar frequency. The estimated error rate of the insertion process of 13% per bp is by far the largest reported in vivo, with the possible exception of somatic hypermutation in the immunoglobulin gene. The data constrain possible mechanisms of microindels and raise the question of whether microindels are 'scars' from the bypass of large DNA adducts by a translesional polymerase, e.g. the 'Tarzan model' presented herein.