Immortal, telomerase-negative cell lines derived from a Li-Fraumeni syndrome patient exhibit telomere length variability and chromosomal and minisatellite instabilities.
Immortal, telomerase-negative cell lines derived from a Li-Fraumeni syndrome patient exhibit telomere length variability and chromosomal and minisatellite instabilities.
复制标题
来自李法美尼综合征患者的永生端粒酶阴性细胞系表现出端粒长度变异性以及染色体和小卫星不稳定性。
DOI：
10.1093/carcin/bgg024
复制
发表时间：
2003
期刊：
影响因子：
4.7
通讯作者：
Barrett,JCarl
中科院分区：
文献类型：
--
作者：
Tsutsui,Takeki;Kumakura,Shin-Ichi;Tamura,Yukiko;Tsutsui,TakeoW;Sekiguchi,Mizuki;Higuchi,Tokihiro;Barrett,JCarl
5个永生细胞系来源于李-弗劳梅尼综合征患者（MDAH 087）与生殖细胞系突变p53等位基因的端粒长度和基因组的不稳定性进行了表征。剩余的野生型53等位基因在细胞系中丢失。所有永生细胞系均未检测到端粒酶活性。每个细胞系的五个亚克隆和每个亚克隆的五个再亚克隆也显示出不可检测的端粒酶活性。所有5个永生细胞系的末端限制性片段（TRFs）的平均长度表现出变异性。每个细胞系的亚克隆和亚克隆的再亚克隆也显示TRF变异性，表明变异性是由于克隆异质性。在这些细胞系（包括亚克隆和再亚克隆）中观察到高频率的染色体畸变，主要类型为断裂、双微小染色体和双着丝粒染色体。此外，在永生细胞系中观察到DNA指纹检测到的小卫星不稳定性。然而，所有的细胞系均为微卫星不稳定性阴性。由于认为小卫星序列在哺乳动物细胞中是重组原性的，因此这些结果表明在这些细胞系中重组率可以增加。同样缺乏p53功能的肿瘤来源的人类细胞系HT 1080细胞和HeLa细胞表现出很少的涉及染色体和小卫星不稳定性的基因组不稳定性，这表明在缺乏端粒酶活性的永生细胞系中观察到的染色体和小卫星不稳定性可能不是由p53功能的丧失引起的。
Five immortal cell lines derived from a Li-Fraumeni syndrome patient (MDAH 087) with a germline mutantp53allele were characterized with respect to telomere length and genomic instability. The remaining wild-typep53allele is lost in the cell lines. Telomerase activity was undetectable in all immortal cell lines. Five subclones of each cell line and five re-subclones of each of the subclones also showed undetectable telomerase activity. All five immortal cell lines exhibited variability in the mean length of terminal restriction fragments (TRFs). Subclones of each cell line, and re-subclones of the subclones also showed TRF variability, indicating that the variability is owing to clonal heterogeneity. Chromosome aberrations were observed at high frequencies in these cell lines including the subclones and re-subclones, and the principal types of aberrations were breaks, double minute chromosomes and dicentric chromosomes. In addition, minisatellite instability detected by DNA fingerprints was observed in the immortal cell lines. However, all of the cell lines were negative for microsatellite instability. As minisatellite sequences are considered recombinogenic in mammalian cells, these results suggest that recombination rates can be increased in these cell lines. Tumor-derived human cell lines, HT1080 cells and HeLa cells that also lackp53function, exhibited little genomic instability involving chromosomal and minisatellite instabilities, indicating that chromosomal and minisatellite instabilities observed in the immortal cell lines lacking telomerase activity could not result from loss ofp53function.