Common fragile sites and cancer -: Targeted cloning by insertional mutagenesis
Common fragile sites and cancer -: Targeted cloning by insertional mutagenesis
复制标题
DOI：
10.1196/annals.1322.002
复制
发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Schwab, M
中科院分区：
文献类型：
--
作者：
B端ttel, I;Fechter, A;Schwab, M
遗传不稳定性是致癌和肿瘤发生的一个重要方面，产生染色体变异和广泛的肿瘤内异质性。常见的脆性位点是预定的染色体断裂区域。在实验中，它们可以被证明是在复制胁迫条件下中期染色体上出现的位点特异性间隙或断裂。多年来，它们一直被认为是遗传不稳定的染色体表达，并被认为与癌症的致病作用有关。然而，常见的脆弱位点仍然是人类染色体固有的神秘部分，大多数脆弱位点的DNA序列迄今尚未确定。通过外源标记基因插入诱变对脆弱位点DNA进行遗传标记的想法为大量常见脆弱位点的高效靶向克隆提供了平台。
Genetic instability is an important facet of carcinogenesis and oncogenesis, generating chromosomal variability and extensive intratumor heterogeneity. Common fragile sites are predetermined chromosomal breakage regions. Experimentally, they can be demonstrated as site-specific gaps or breaks seen on metaphase chromosomes under conditions of replicative stress. They have been known for many years as a chromosomal expression of genetic instability and have been implicated to have a causative role in cancer. However, common fragile sites still remain enigmatic intrinsic parts of human chromosomes, and the DNA sequences at most of the fragile sites have noot been identified so far. The idea of genetically tagging fragile site DNA by insertional mutagenesis through an exogenous marker gene has provided a platform for the efficient targeted cloning of a substantial number of common fragile sites.