Ribas Maria, Masramon Laia, Aiza Gemma, Capellà Gabriel, Miró Rosa, Peinado Miguel A
Institut de Recerca Oncològica, Hospital Duran i Reynals, Barcelona, Spain.
FASEB J. 2003 Feb;17(2):289-91. doi: 10.1096/fj.02-0425fje. Epub 2002 Dec 3.
Biological and genetic cell heterogeneity is a landmark of most colorectal cancers and provides a frame for tumor progression as an evolutional process. Classical models have hypothesized that increased genetic instability may contribute to modulating and shaping malignant transformation. This is true for the small subset of colorectal cancers displaying microsatellite instability. For the rest of colorectal tumors, numerical and/or structural chromosomal alterations are the most prominent outcome of genetic disruption. These observations have prompted some investigators to hypothesize about the presence of chromosomal instability in these cells. To characterize chromosomal instability in cancer cells, we have analyzed genetic clonal divergence in three colorectal cancer cell lines considered to be archetypes in cancer research (HCT116, LoVo, and SW480). A dynamic setting was designed to allow the calculation of mutation rates. Comprehensive analyses at the chromosomal level revealed distinctive patterns of genetic divergence. Aneuploid SW480 cells displayed high rates of structural alterations (>100-fold) as compared with near diploid LoVo cells. Numerical alterations also occurred more frequently in SW480 cells but at low rates as compared with rearrangements in the chromosomically unstable SW480 cells. These results strengthen the role of structural instability in the generation of genetic heterogeneity in colorectal cancer.
生物学和基因细胞异质性是大多数结直肠癌的一个标志，并为肿瘤进展这一进化过程提供了一个框架。经典模型曾假设，遗传不稳定性增加可能有助于调节和塑造恶性转化。对于显示微卫星不稳定性的一小部分结直肠癌来说确实如此。对于其余的结直肠肿瘤，染色体数目和/或结构改变是基因破坏最显著的结果。这些观察结果促使一些研究人员推测这些细胞中存在染色体不稳定性。为了表征癌细胞中的染色体不稳定性，我们分析了三种在癌症研究中被视为原型的结直肠癌细胞系（HCT116、LoVo和SW480）中的基因克隆差异。设计了一个动态环境以允许计算突变率。在染色体水平的综合分析揭示了独特的基因差异模式。与近二倍体的LoVo细胞相比，非整倍体的SW480细胞显示出较高的结构改变率（>100倍）。染色体数目改变在SW480细胞中也更频繁地发生，但与染色体不稳定的SW480细胞中的重排相比发生率较低。这些结果强化了结构不稳定性在结直肠癌基因异质性产生中的作用。
