DNA C-circles are specific and quantifiable markers of alternative-lengthening-of-telomeres activity
DNA C-circles are specific and quantifiable markers of alternative-lengthening-of-telomeres activity
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DOI：
10.1038/nbt.1587
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发表时间：
2009-12-01
影响因子：
46.9
通讯作者：
Reddel, Roger R.
中科院分区：
文献类型：
--
作者：
Henson, Jeremy D.;Cao, Ying;Reddel, Roger R.
端粒替代延长机制（ALT）(1)很可能是抗癌治疗的一个重要靶点，因为约10%的癌症依赖这种端粒维持机制来持续生长(2)，并且抑制ALT可导致细胞衰老(3)。然而，由于缺乏合适的ALT活性检测方法以及已知的ALT特异性靶分子，目前还没有开发出用于治疗的ALT抑制剂。在此我们表明，部分单链端粒(CCCTAA)ₙ DNA环（C - 环）是ALT特异性的。我们提供了一种对ALT活性具有快速线性响应且适用于筛选ALT抑制剂的检测方法。我们在ALT(+)骨肉瘤患者的血液中检测到C - 环，这表明C - 环检测（CC检测）可能在ALT(+)肿瘤的诊断和治疗方面具有临床应用价值。
Alternative lengthening of telomeres (ALT)(1) is likely to be an important target for anticancer treatment as similar to 10% of cancers depend on this telomere maintenance mechanism for continued growth(2), and inhibition of ALT can cause cellular senescence(3). However, no ALT inhibitors have been developed for therapeutic use because of the lack of a suitable ALT activity assay and of known ALT-specific target molecules. Here we show that partially single-stranded telomeric (CCCTAA)(n) DNA circles (C-circles) are ALT specific. We provide an assay that is rapidly and linearly responsive to ALT activity and that is suitable for screening for ALT inhibitors. We detect C-circles in blood from ALT(+) osteosarcoma patients, suggesting that the C-circle assay (CC assay) may have clinical utility for diagnosis and management of ALT(+) tumors.