Children's Medical Research Institute, University of Sydney, New South Wales, Australia.
Nat Biotechnol. 2009 Dec;27(12):1181-5. doi: 10.1038/nbt.1587.
Alternative lengthening of telomeres (ALT) is likely to be an important target for anticancer treatment as approximately 10% of cancers depend on this telomere maintenance mechanism for continued growth, and inhibition of ALT can cause cellular senescence. 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.
端粒的替代性延长（ALT）可能是癌症治疗的一个重要靶点，因为大约 10%的癌症依赖这种端粒维持机制来持续生长，而抑制 ALT 会导致细胞衰老。然而，由于缺乏合适的 ALT 活性测定方法和已知的 ALT 特异性靶分子，尚未开发出用于治疗用途的 ALT 抑制剂。在这里，我们证明部分单链端粒（CCCTAA）（n）DNA 环（C 环）是 ALT 特异性的。我们提供了一种快速且线性响应 ALT 活性的测定方法，适用于筛选 ALT 抑制剂。我们在 ALT（+）骨肉瘤患者的血液中检测到 C 环，这表明 C 环测定（CC 测定）可能具有用于 ALT（+）肿瘤的诊断和管理的临床应用价值。
