Integration of new DNA into a cellular chromosome can alter the activity of nearby genes, sometimes affecting subsequent cell growth. A potent form of insertional mutagenesis involves integration of retroviral DNA produced by reverse transcription, a required step in the replication of retroviruses. In recent years retroviral replication has been adapted to allow new gene addition by retroviral vectors. Early in the history of retrovirus research, analysis of insertional mutagenesis in laboratory animals was found at times to result in transformation, leading to the discovery of cellular proto-oncogenes. In-depth analysis of the genetic consequences showed that integration of retroviral DNA could alter the gene activity in a variety of ways. Mechanisms of retroviral insertional mutagenesis in humans are much less well documented. However, recent work from the gene therapy and HIV fields now specify four genetic mechanisms of retroviral insertional mutagenesis in humans: (1) gene activation by integration of an enhancer sequence encoded in a retroviral vector (enhancer insertion), (2) gene activation by promoter insertion, (3) gene inactivation by insertional disruption, and (4) gene activation by mRNA 3' end substitution. In each example, integration in patients was associated with clonal expansion or frank transformation.

中文翻译：

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人类逆转录病毒诱变：促进细胞克隆扩展的四个遗传机制的证据。

新DNA整合入细胞染色体可以改变附近基因的活性，有时会影响随后的细胞生长。一种有效的插入诱变形式涉及整合由逆转录产生的逆转录病毒DNA，这是逆转录病毒复制中的必要步骤。近年来，逆转录病毒复制已被适应以允许逆转录病毒载体添加新基因。在逆转录病毒研究的早期，有时会发现对实验动物的插入诱变进行分析以进行转化，从而发现了细胞原癌基因。对遗传后果的深入分析表明，逆转录病毒DNA的整合可以多种方式改变基因活性。在人类中逆转录病毒插入诱变的机制尚缺乏很好的文献记载。然而，基因治疗和HIV领域的最新工作现在确定了人类逆转录病毒插入诱变的四个遗传机制：（1）通过整合逆转录病毒载体中编码的增强子序列进行基因激活（增强子插入），（2）通过启动子插入进行基因激活，（3）通过插入破坏使基因失活，以及（4）通过mRNA 3'末端取代来激活基因。在每个实例中，患者的整合与克隆扩增或坦率转化有关。（4）通过mRNA 3'末端取代的基因激活。在每个实例中，患者的整合与克隆扩增或坦率转化有关。（4）通过mRNA 3'末端取代的基因激活。在每个实例中，患者的整合与克隆扩增或坦率转化有关。