Mutator phenotype in cancer: Timing and perspectives
Mutator phenotype in cancer: Timing and perspectives
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DOI：
10.1002/em.20111
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发表时间：
2005-03-01
影响因子：
2.8
通讯作者：
Loeb, LA
中科院分区：
文献类型：
--
作者：
Bielas, JH;Loeb, LA
正常的人类细胞以非凡的准确性复制它们的DNA。在每个分裂周期中，每个子细胞都会收到完整而准确的遗传信息。据估计，每聚合10(9)到10(10)个核苷酸，在DNA复制过程中大约会发生一个错误。干细胞是癌症的前体细胞，可能会更准确地复制它们的基因。相比之下，构成肿瘤的恶性细胞具有明显的异质性，并表现出多种染色体异常和DNA核苷酸序列的变化。为了解释正常细胞中罕见的突变和癌症中存在的大量突变之间的差异，我们最初假设在肿瘤进展过程中，癌细胞必须表现出突变表型。在这一方面，我们总结了支持人类癌症突变子表型的证据，分析了最近对人类癌症突变的测量，考虑了突变子表型的表达时机，并集中在人类肿瘤中大量随机突变的重要后果。环境。摩尔。诱变剂。45：206-213,2005。(C)2005年Wiley-Liss，Inc.
Normal human cells replicate their DNA with exceptional accuracy. During every division cycle, each daughter cell receives a full and accurate complement of genetic information. It has been estimated that approximately one error occurs during DNA replication for each 10(9) to 10(10) nucleotides polymerized. Stem cells, the cells that are progenitors of cancer, may replicate their genes even more accurately. In contrast, the malignant cells that constitute a tumor are markedly heterogeneous and exhibit multiple chromosomal abnormalities and alterations in the nucleotide sequence of DNA. To account for the disparity between the rarity of mutations in normal cells and the large numbers of mutations present in cancer, we initially hypothesized that during tumor progression, cancer cells must exhibit a mutator phenotype. In this perspective, we summarize the evidence supporting a mutator phenotype in human cancer, analyze recent measurements of mutations in human cancer, consider the timing for the expression of a mutator phenotype, and focus on the important consequences of large numbers of random mutations in human tumors. Environ. Mol. Mutagen. 45:206-213, 2005. (c) 2005 Wiley-Liss, Inc.