Spectral karyotyping suggests additional subsets of colorectal cancers characterized by pattern of chromosome rearrangement
Spectral karyotyping suggests additional subsets of colorectal cancers characterized by pattern of chromosome rearrangement
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DOI：
10.1073/pnas.041603298
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发表时间：
2001-02-27
影响因子：
11.1
通讯作者：
Edwards, PAW
中科院分区：
文献类型：
--
作者：
Abdel-Rahman, WM;Katsura, K;Edwards, PAW
大多数肿瘤中大量的染色体异常可能反映了肿瘤中存在的基因组不稳定性，因此染色体异常的模式和变异性将结合选择效应反映不稳定性的机制。研究了17种结直肠癌来源细胞系的染色体重排。比较基因组杂交表明，染色体的变化是原发肿瘤中发现的具有代表性的变化。光谱核型分析（SKY）表明，易位变化很大，而且大多不平衡，易位不超过3个系。至少可以区分出三种核型模式。部分系染色体异常较少，均表现为微卫星不稳定性、复制错误(RER)+表型。大多数系有许多染色体异常：至少有7个表现出令人惊讶的一致模式，其特征是多重不平衡易位和中期变异，染色体数量在三倍体左右，6-16个结构畸变，并且在获得和失去方面相似。几乎所有这些都是RER-，但有一个LS411是RER+。HCA7系表现出一种新的模式，表明存在第三种基因组不稳定性：多重互惠易位，几乎没有数值变化或可变性。这条线也是RER+。如果在肿瘤进化过程中选择较远的潜在缺陷，两种基因组不稳定性在一个肿瘤中共存是可以预期的。
The abundant chromosome abnormalities in most carcinomas are probably a reflection of genomic instability present in the tumor, so the pattern and variability of chromosome abnormalities will reflect the mechanism of instability combined with the effects of selection. Chromosome rearrangement was investigated in 17 colorectal carcinoma-derived cell lines. Comparative genomic hybridization showed that the chromosome changes were representative of those found in primary tumors. Spectral karyotyping (SKY) showed that translocations were very varied and mostly unbalanced, with no translocation occurring in more than three lines. At least three karyotype patterns could be distinguished. Some lines had few chromosome abnormalities: they all showed microsatellite instability, the replication error (RER)+ phenotype. Most lines had many chromosome abnormalities: at least seven showed a surprisingly consistent pattern, characterized by multiple unbalanced translocations and intermetaphase variation, with chromosome numbers around triploid, 6-16 structural aberrations, and similarities in gains and losses. Almost all of these were RER-, but one, LS411, was RER+. The line HCA7 showed a novel pattern, suggesting a third kind of genomic instability: multiple reciprocal translocations, with little numerical change or variability. This line was also RER+. The coexistence in one tumor of two kinds of genomic instability is to be expected if the underlying defects are selected far in tumor evolution.