Department of Pathology, Dunedin School of Medicine, Health Sciences, University of Otago, Dunedin, New Zealand.
J Pathol. 2012 Feb;226(3):509-18. doi: 10.1002/path.2981. Epub 2012 Jan 4.
The alternative lengthening of telomeres (ALT) mechanism represents an alternative to the enzyme telomerase in the maintenance of mammalian telomeres in 25-60% of sarcomas and a minority of carcinomas (about 5-15%). ALT-positive cells are distinguished by long and heterogeneous telomere length distributions by terminal restriction fragment (TRF) Southern blotting. Another diagnostic marker of ALT is discrete nuclear co-localized signals of telomeric DNA and the promyelocytic leukaemia protein (PML), referred to as ALT-associated PML bodies (APBs). Recently, we detected smaller sized co-localized PML and telomere DNA (APB-like) bodies in endothelial cells adjacent to astrocytoma tumour cells in situ. In this study, we examined a wide variety of non-neoplastic tissues, and report that co-localized signals of PML and telomere DNA are present in endothelial, stromal, and some epithelial cells. Co-localized signals of PML and telomere DNA showed an increased frequency in non-neoplastic cells with DNA damage. These results suggest that a mechanism similar to that in ALT-positive tumours also operates in non-neoplastic cells, which may be activated by DNA damage.
端粒的非经典延长（ALT）机制代表了在 25-60%的肉瘤和少数癌症（约 5-15%）中维持哺乳动物端粒的酶端粒酶的另一种选择。ALT 阳性细胞通过末端限制片段（TRF）Southern 印迹法区分出长而不均匀的端粒长度分布。ALT 的另一个诊断标志物是端粒 DNA 和早幼粒细胞白血病蛋白（PML）的离散核共定位信号，称为 ALT 相关 PML 体（APB）。最近，我们在原位星形细胞瘤肿瘤细胞附近的内皮细胞中检测到较小的共定位 PML 和端粒 DNA（APB 样）体。在这项研究中，我们检查了多种非肿瘤组织，并报告说 PML 和端粒 DNA 的共定位信号存在于内皮细胞、基质细胞和一些上皮细胞中。具有 DNA 损伤的非肿瘤细胞中 PML 和端粒 DNA 的共定位信号的频率增加。这些结果表明，类似于 ALT 阳性肿瘤中的机制也在非肿瘤细胞中起作用，该机制可能被 DNA 损伤激活。
