Evolutionary hypothesis of telomere length in primary breast cancer and brain tumour patients: a tracer for genomic—tumour heterogeneity and instability

Evolutionary hypothesis of telomere length in primary breast cancer and brain tumour patients: a tracer for genomic—tumour heterogeneity and instability
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原发性乳腺癌和脑肿瘤患者端粒长度的进化假说:基因组肿瘤异质性和不稳定性的示踪剂

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发表时间:
2011
影响因子:
3.9
通讯作者:
M. Atri
M. Atri
中科院分区:
生物学4区
文献类型:
--
作者:
P. Mehdipour;M. Kheirollahi;M. Mehrazin;N. Kamalian;M. Atri

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以前有报道说,肿瘤样本的端粒比周围正常组织的端粒短。因此,可以注意到恶性组织与端粒行为之间相关性的初步迹象。将生殖细胞和体细胞之间的知识联系起来可以促进对细胞进化的理解。我们研究的目的是为原发性BC(乳腺癌)和BTs(脑肿瘤)中TL(端粒长度)的进化假说提供证据,这可能被用作预后和/或预测标志物。用高纯度PCR模板制备试剂盒从冷冻组织中提取DNA。使用Telo TTAGGG端粒长度测定试剂盒(一种非放射性荧光测定)的标准方案。通过免疫荧光分析提取的细胞中的蛋白质表达。同时检测端粒酶活性。在原发性BC和原发性BT患者中,TL的G/T(基因组/肿瘤比)在BC患者(P=0.025)和BT患者(P=0.001)中均显示出显著差异。通过Q-FISH(定量荧光原位杂交)检测的端粒信号模式显示,在所有样本中,除一个样本外,无论是BC患者还是BT患者,与血液相关的组织中SI(信号强度)均显著降低(0.041≥P≥0.001)。然而,Q-FISH获得的数据支持Southern印迹的结果。这些数据反映了BC或BT患者的显著多样性,为TL在癌症发展和进展中的进化假说提供了证据。
It was previously reported that tumour samples had shorter telomeres than the surrounding normal tissue. Hereby, the initial sign of correlation between malignant tissue and telomere behaviour could be noticed. Bridging knowledge between germ and somatic cells could facilitate understanding cellular evolution. The aim of our investigation was to provide evidence for the evolutionary hypothesis of TL (telomere length) in primary BC (breast cancer) and BTs (brain tumours), which might be applied as a prognostic and/or predictive marker. DNA extraction from the frozen tissues was performed using high pure PCR template preparation kit. Standard protocol of Telo TTAGGG Telomere Length Assay kit, a non‐radioactive chemiluminescent assay, was used. The protein expression in extracted cells was analysed by immunofluorescence. We also detected telomerase activity. The G/T (genomic/tumour ratio) for TL in two groups of patients affected with primary BC and primary BT revealed significant differences in both BC patients (P=0.025) and in BTs (P=0.001). The pattern of telomere signals by Q‐FISH (quantitative fluorescent in situ hybridization) show that in all samples, except one, SI (signal intensity) has been significantly decreased in tissue related to blood, either in BC patients or in patients with BTs (0.041≥P≥0.001). However, the data achieved by Q‐FISH support the results of Southern blot. These data reflect a significant diversity either in BC or in BT patients, providing evidence for the evolutionary hypothesis of TL in cancer development and progression.
DOI: 10.1073/pnas.95.10.5607
发表时间: 1998-05-12
影响因子: 11.1
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