Chromosome number and structure both are markedly stable in RER colorectal cancers and are not destabilized by mutation of p53
Chromosome number and structure both are markedly stable in RER colorectal cancers and are not destabilized by mutation of p53
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DOI：
10.1038/sj.onc.1201986
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发表时间：
1998-08-13
期刊：
影响因子：
8
通讯作者：
Markowitz, SD
中科院分区：
文献类型：
--
作者：
Eshleman, JR;Casey, G;Markowitz, SD
根据是否存在微卫星不稳定性对14个结直肠癌细胞系进行了进一步的染色体稳定性分析，结果表明，非RER(微卫星稳定)细胞系具有高度异常的核型，不仅染色体数目发生改变，而且染色体结构也发生改变，包括染色体缺失、倒位和易位。相比之下，微卫星不稳定(RER)细胞系的染色体数目变化明显较少，此外，RER细胞系的细胞遗传学明显染色体结构变化也明显较少，与非RER结肠癌相比，RER结肠癌发生染色体获得、丢失或断裂的可能性显著降低。通过基因测序鉴定P53基因状态，以确定P53基因状态是否与RER癌的染色体稳定性相关。P53基因突变在所有非RER结肠癌中都存在，但在9例RER结肠癌中也有4例存在P53基因突变，意外的是，携带突变型P53的RER结肠癌表现出与携带野生型P53的RER结肠癌相同的染色体数量稳定性和染色体结构稳定性，因此，在RER结肠癌中，特异的P53独立机制积极地维持了染色体数量和结构的稳定。
Fourteen colorectal cancer cell lines, categorized according to the presence or absence of microsatellite instability, were further analysed tor chromosomal stability by karyotyping, NonRER (microsatellite stable) cell lines typically displayed highly aberrant karyotypes with alterations not only of chromosome number but also of chromosome structure including chromosomal deletions, inversions, and translocations. RER (microsatellite unstable) cell lines, in contrast, displayed significantly fewer alterations of chromosome number, Moreover, RER cell lines also displayed significantly fewer cytogenetically evident alterations of chromosome structure, Compared to NonRER colon cancers, RER colon cancers are significantly less likely to have undergone chromosomal gain, loss, or breakage. Characterization of p53 gene status by gene sequencing was performed in an attempt to determine if p53 gene status correlated with the chromosomal stability of the RER cancers. Gene mutations in p53 were present in all of the NonRER colon cancers, However, p53 gene mutations were also found present in four of nine of the RER colon cancers, Unexpectedly, RER colon cancers bearing mutant p53 demonstrated the same stability of chromosome number, and the same stability of chromosome structure, as the RER colon cancers with wild-type p53, Therefore, in RER colon cancers specific p53 independent mechanisms actively maintain the stability of both chromosome number and structure.