New approaches to understanding p53 gene tumor mutation spectra
New approaches to understanding p53 gene tumor mutation spectra
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DOI：
10.1016/s0027-5107(99)00162-1
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发表时间：
1999-12-17
影响因子：
2.3
通讯作者：
Hainaut, P
中科院分区：
文献类型：
--
作者：
Hollstein, M;Hergenhahn, M;Hainaut, P
十年前，Baker等人描述了人类肿瘤中出现的第一个p53基因突变[S. J. Baker，E.R. Fearon，J.M. Nigro，S.R.汉密尔顿，AC Preisinger，J.M.杰瑟普，P，货车Tuinen，D.H. Ledbetter，D.F. Barker，Y.中村河白色。B。Vogelstein，Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas，Science 244（1989）217-221]。现在在人p53肿瘤突变的IARC数据库中有超过10，000个从公开文献中提取的突变[P.海诺，T.埃尔南德斯。A.罗宾逊，P.弗洛雷斯，M. Hollstein，C.C.哈里斯河，巴西-地蒙泰萨诺，IARC database of p53 gene mutations in human tumors and cell lines：updated compilation，revised formats and new visualization tools，Nucleic Acids Res.26（1998）205-213; Version R3，January 1999]。癌症患者中大量不同的肿瘤突变集合提供了关于作为人类基因突变的重要原因的环境因素或生物学过程的性质的重要信息，因为外源性诱变剂以及遗传变化的内源性机制在靶DNA中产生特征类型的模式[J.H.米勒，细菌的突变特异性，Annu. Rev. Genet. 17（1983）215-238; T. Lindahl，DNA一级结构的不稳定性和衰变，Nature 362（1993）709-715：S. P. Hussain，C.C. Harris，人类癌症的分子流行病学：肿瘤抑制基因突变谱研究的贡献，癌症研究58（1998）4023-4037; P.海诺，M. Hollstein，p53 and human cancer：the first ten thousand mutations，Adv. Cancer Res.2000]。癌症中的P53基因突变可以与来自具有已知暴露史的患者或健康个体的人淋巴细胞的HPRT基因座处的点突变谱进行比较，积累的数据表明，这两个基因座的突变模式具有某些共同的特征。通过比较特定患者组的典型p53肿瘤突变与实验产生的突变，可以检验关于特定癌症风险因素的假设。啮齿动物或体外原核和真核细胞中。正在探索这种假设检验方法的改进，即采用人工引入实验室诱变测定中使用的实验生物体中的人p53序列。P53特异性实验室模型，结合设计用于高通量突变筛查的DNA微芯片，有望揭示目前隐藏在人类肿瘤p53突变编辑中的信息。(C)1999 Elsevier Science B. V.保留所有权利。
The first p53 gene mutation arising in a human tumor was described a decade ago by Baker et al. [S.J. Baker, E.R. Fearon, J.M. Nigro, S.R. Hamilton, A.C. Preisinger, J.M. Jessup, P, van Tuinen, D.H. Ledbetter, D.F. Barker, Y. Nakamura, R. White. B. Vogelstein, Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas, Science 244 (1989) 217-221]. There are now over 10,000 mutations extracted from the published literature in the IARC database of human p53 tumor mutations [P. Hainaut, T. Hernandez. A. Robinson, P. Rodriguez-Tome, T. Flores, M. Hollstein, C.C. Harris, R. Montesano, IARC database of p53 gene mutations in human tumors and cell lines: updated compilation, revised formats and new visualization tools, Nucleic Acids Res. 26 (1998) 205-213; Version R3, January 1999]. A large and diverse collection of tumor mutations in cancer patients provides important information on the nature of environmental factors or biological processes that are important causes of human gene mutation, since xenobiotic mutagens as well as endogenous mechanisms of genetic change produce characteristic types of patterns in target DNA [J.H. Miller, Mutational specificity in bacteria, Annu. Rev. Genet. 17 (1983) 215-238; T. Lindahl, Instability and decay of the primary structure of DNA, Nature 362 (1993) 709-715: S.P. Hussain, C.C. Harris, Molecular epidemiology of human cancer: contribution of mutation spectra studies of tumor suppressor genes, Cancer Res. 58 (1998) 4023-4037; P. Hainaut, M. Hollstein, p53 and human cancer: the first ten thousand mutations, Adv. Cancer Res. 2000]. P53 gene mutations in cancers can be compared to point mutation spectra at the HPRT locus of human lymphocytes from patients or healthy individuals with known exposure histories, and accumulated data indicate that mutation patterns at the two loci share certain general features.Hypotheses regarding specific cancer risk factors can be tested by comparing p53 tumor mutations typical of a defined patient group against mutations generated experimentally in rodents or in prokaryotic and eukaryotic cells in vitro. Refinements of this approach to hypothesis testing are being explored that employ human p53 sequences introduced artificially into experimental organisms used in laboratory mutagenesis assays. P53-specific laboratory models, combined with DNA microchips designed for high through-put mutation screening promise to unmask information currently hidden in the compilation of human tumor p53 mutations. (C) 1999 Elsevier Science B.V. All rights reserved.