Weber R G, Bridger J M, Benner A, Weisenberger D, Ehemann V, Reifenberger G, Lichter P
Abteilung Organisation komplexer Genome, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Cytogenet Cell Genet. 1998;83(3-4):266-9. doi: 10.1159/000015168.
Although alterations in chromosome number have frequently been detected in human tumor cells and associated with tumor initiation and progression, the causal mechanisms are still not understood. One protein known to be involved in maintaining genetic stability is tumor suppressor p53. In mice, p53 has been implicated in the maintenance of diploidy (Cross et al., 1995) and the regulation of centrosome duplication (Fukasawa et al., 1996). Here we report on cerebral primitive neuroectodermal tumors that lacked the wild-type p53 gene (TP53) and showed multiple numerical chromosome aberrations, as detected by comparative genomic hybridization. In these tumors, the centrosome number was significantly higher than in a control tumor without a detected TP53 mutation and with few chromosomal imbalances. These findings indicate that abnormal centrosome amplification can occur in human tumors lacking wild-type TP53 and may be a mechanism by which numerical chromosome aberrations are generated.
虽然在人类肿瘤细胞中经常检测到染色体数目改变，并与肿瘤的发生和进展相关，但其因果机制仍不清楚。一种已知参与维持遗传稳定性的蛋白质是肿瘤抑制因子p53。在小鼠中，p53与维持二倍体状态（Cross等人，1995年）和中心体复制的调控有关（Fukasawa等人，1996年）。在此，我们报告了通过比较基因组杂交检测到的缺乏野生型p53基因（TP53）并显示出多个染色体数目畸变的脑原始神经外胚层肿瘤。在这些肿瘤中，中心体数量明显高于未检测到TP53突变且染色体失衡较少的对照肿瘤。这些发现表明，在缺乏野生型TP53的人类肿瘤中可能会发生异常的中心体扩增，并且这可能是产生染色体数目畸变的一种机制。
