Izumi Hideki, Hara Takahiko, Oga Atsunori, Matsuda Kenji, Sato Yuko, Naito Katsusuke, Sasaki Kohsuke
Neoplasia. 2002 Mar-Apr;4(2):103-11. doi: 10.1038/sj.neo.7900205.
Malignant tumors have telomerase activity, which is thought to play a critical role in tumor growth. However, the relation between telomerase activity and genomic DNA status in tumor cells is poorly understood. In the present study, we examined telomerase activity in 13 clear cell type renal cell carcinomas (CRCCs) with similar clinicopathologic features by telomeric repeat amplification protocol assay (TRAP). Based on TRAP assay results, we divided the CRCCs into two groups: a high telomerase activity group and a low/no telomerase activity group. We then analyzed genomic aberration, DNA ploidy, and telomere status in these two groups by comparative genomic hybridization (CGH), laser scanning cytometry (LSC), and telomere-specific fluorescence in situ hybridization (T-FISH), respectively. CGH showed the high telomerase activity group to have fewer genomic changes than the low/no telomerase activity group, which had many genomic aberrations. Moreover, with LSC, DNA diploid cells were found more frequently in the high telomerase activity group than in the low/no telomerase activity group. In addition, T-FISH revealed strong telomere signal intensity in the high telomerase activity group compared with that of the low/no telomerase activity group. These results suggest that telomerase activity is linked to genomic DNA status and that high telomerase activity is associated with genomic stability, DNA ploidy, and telomere length in CRCC.
恶性肿瘤具有端粒酶活性,这被认为在肿瘤生长中起关键作用。然而,肿瘤细胞中端粒酶活性与基因组DNA状态之间的关系尚不清楚。在本研究中,我们通过端粒重复序列扩增法(TRAP)检测了13例具有相似临床病理特征的透明细胞型肾细胞癌(CRCC)的端粒酶活性。根据TRAP检测结果,我们将CRCC分为两组:高端粒酶活性组和低/无端粒酶活性组。然后,我们分别通过比较基因组杂交(CGH)、激光扫描细胞术(LSC)和端粒特异性荧光原位杂交(T-FISH)分析了这两组的基因组畸变、DNA倍体和端粒状态。CGH显示,高端粒酶活性组的基因组变化比低/无端粒酶活性组少,后者有许多基因组畸变。此外,通过LSC发现,高端粒酶活性组中DNA二倍体细胞的出现频率高于低/无端粒酶活性组。另外,T-FISH显示,与低/无端粒酶活性组相比,高端粒酶活性组的端粒信号强度更强。这些结果表明,端粒酶活性与基因组DNA状态有关,并且高端粒酶活性与CRCC中的基因组稳定性、DNA倍体和端粒长度相关。