Genetic instability in colorectal cancers
Genetic instability in colorectal cancers
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DOI：
10.1038/386623a0
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发表时间：
1997-04-10
期刊：
影响因子：
64.8
通讯作者：
Vogelstein, B
中科院分区：
文献类型：
--
作者：
Lengauer, C;Kinzler, KW;Vogelstein, B
长期以来，人们一直认为遗传不稳定是人类肿瘤不可或缺的组成部分(1-3)，在一小部分肿瘤中，错配修复缺陷导致核苷酸序列水平的微卫星不稳定(4，5)，在其他肿瘤中，染色体数量异常(非整倍体)表明不稳定，但假设不稳定的性质和大小尚有待猜测。我们在这里表明，没有微卫星不稳定性的结直肠肿瘤在染色体分离方面表现出显著的缺陷，导致每代人每条染色体的得失超过10(-2)。这种形式的染色体不稳定反映了一种持续的细胞缺陷，这种缺陷在肿瘤细胞的整个生命周期中持续存在，而不仅仅是与染色体数量有关。虽然微卫星不稳定是一种隐性特征(6，7)，但染色体不稳定似乎是显性的，这些数据表明，持续的遗传不稳定可能是所有结直肠癌发展的关键，这种不稳定可以通过两种不同的途径产生。
It has long been considered that genetic instability is an integral component of human neoplasia(1-3), In a small fraction of tumours, mismatch repair deficiency leads to a microsatellite instability at the nucleotide sequence level(4,5), In other tumours, an abnormal chromosome number (aneuploidy) has suggested an instability, but the nature and magnitude of the postulated instability is a matter of conjecture. We show here that colorectal tumours without microsatellite instability exhibit a striking defect in chromosome segregation, resulting in gains or losses in excess of 10(-2) per chromosome per generation. This form of chromosomal instability reflected a continuing cellular defect that persisted throughout the lifetime of the tumour cell and was not simply related to chromosome number. While microsatellite instability is a recessive trait(6,7), chromosomal instability appeared to be dominant, These data indicate that persistent genetic instability may be critical for the development of all colorectal cancers, and that such instability can arise through two distinct pathways.