文章：

末端连接，易位和癌症

End-joining, translocations and cancer

原文发布日期：2013-06-13

DOI: 10.1038/nrc3537

类型: Review Article

开放获取: 否

要点：

1. Translocations that create neomorphic fusion genes occur in both lymphoid malignancies and solid tumours.
2. A large number of translocations do not encode fusion genes and may not contribute to malignancy.
3. Translocations frequently contain complex, clustered sequence rearrangements, similar to chromothrypsis, and may also contain genetic material from several different chromosomes.
4. Many translocations arise as a consequence of 'classical' or 'alternative' pathways of non-homologous end-joining.
5. Mammalian cells have regulatory systems to bias DNA repair towards repair pathways that are less likely to contribute to translocation.
6. Frequency of DNA breakage is the metric that best predicts the likelihood of a particular genomic site being involved in a translocation.
7. Therapeutic intervention to reduce translocation frequency is a potential mechanism for reducing the risk of cancer.

要点翻译：

1. 导致新形态融合基因产生的染色体易位既发生于淋巴样恶性肿瘤，也见于实体瘤。
2. 许多染色体易位并不编码融合基因，且可能不参与恶性病变。
3. 易位染色体常包含复杂的、成簇的序列重排，类似于染色体碎裂现象，也可能含有来自多个不同染色体的遗传物质。
4. 多数染色体易位是“经典”或“替代”非同源末端连接修复途径作用的结果。
5. 哺乳动物细胞具有调控系统，能将DNA修复导向不易引发易位的修复途径。
6. DNA断裂频率是预测特定基因组位点发生易位可能性的最佳指标。
7. 通过治疗干预降低染色体易位频率，是减少癌症风险的潜在机制。

英文摘要：

Fusion genes that are caused by chromosome translocations have been recognized for several decades as drivers of deregulated cell growth in certain types of cancer. In recent years, oncogenic fusion genes have been found in many haematological and solid tumours, demonstrating that translocations are a common cause of malignancy. Sequencing approaches have now confirmed that numerous, non-clonal translocations are a typical feature of cancer cells. These chromosome rearrangements are often highly complex and contain DNA sequence from multiple genomic sites. The factors and pathways that promote translocations are becoming clearer, with non-homologous end-joining implicated as a key source of genomic rearrangements.

摘要翻译： 

由染色体易位导致的融合基因已被认识数十年，被认为是某些类型癌细胞异常增长的驱动因素。近年来，在多种血液系统和实体瘤中发现了致癌性融合基因，表明易位是恶性肿瘤的常见原因。测序方法现已证实，大量非克隆性易位是癌细胞的典型特征。这些染色体重排通常高度复杂，包含来自多个基因组位点的DNA序列。促进易位的因素和通路正逐渐明晰，其中非同源末端连接被认为是基因组重排的关键来源。

原文链接：

End-joining, translocations and cancer