Royle N J, Foxon J, Jeyapalan J N, Mendez-Bermudez A, Novo C L, Williams J, Cotton V E
Department of Genetics, University of Leicester, Leicester, UK.
Cytogenet Genome Res. 2008;122(3-4):281-91. doi: 10.1159/000167814. Epub 2009 Jan 30.
The Alternative Lengthening of Telomeres (ALT) mechanism is utilised by approximately 10% of human tumours and a higher proportion of some types of sarcomas. ALT+ cell lines and tumours show heterogeneous telomere length, extra-chromosomal circular and linear telomeric DNA, ALT associated promyelocytic bodies (APBs), a high frequency of post-replication exchanges in telomeres (designated as telomere-sister chromatid exchanges, T-SCE) and high instability at a GC-rich minisatellite, MS32 (D1S8). It is clear that there is a link between the minisatellite instability and the mechanism that underpins ALT, however currently the nature of this relationship is uncertain. Single molecule analysis of telomeric DNA from ALT+ cell lines and tumours has revealed complex telomere mutations that have not been seen in cell lines or tumours that express telomerase. These complex telomere mutations cannot be explained by T-SCE but must arise by another inter-molecular process. The break-induced replication (BIR) model that may explain the observed high frequency of T-SCE and the presence of complex telomere mutations is reviewed.
端粒替代延长（ALT）机制在约10%的人类肿瘤以及更高比例的某些类型肉瘤中被利用。ALT阳性细胞系和肿瘤表现出端粒长度的异质性、染色体外环状和线性端粒DNA、ALT相关早幼粒细胞体（APB）、端粒复制后交换的高频率（称为端粒姐妹染色单体交换，T-SCE）以及富含GC的小卫星MS32（D1S8）处的高不稳定性。很明显，小卫星不稳定性与支撑ALT的机制之间存在联系，然而目前这种关系的本质尚不确定。对ALT阳性细胞系和肿瘤的端粒DNA进行的单分子分析揭示了复杂的端粒突变，这些突变在表达端粒酶的细胞系或肿瘤中未见。这些复杂的端粒突变无法用T-SCE来解释，而必定是由另一种分子间过程产生的。本文综述了可能解释观察到的T-SCE高频率以及复杂端粒突变存在的断裂诱导复制（BIR）模型。
