文章：

易位和基因融合对癌症成因的影响

The impact of translocations and gene fusions on cancer causation

原文发布日期：2007-03-15

DOI: 10.1038/nrc2091

类型: Review Article

开放获取: 否

要点：

1. Chromosome aberrations are a characteristic feature of neoplasia, and acquired chromosome changes have now been reported in more than 50,000 cases across all main cancer types.
2. Recurrent balanced chromosome rearrangements, in particular translocations, are strongly associated with distinct tumour entities, and there is compelling evidence that they represent an initial event in oncogenesis.
3. Balanced chromosome abnormalities result in the formation of gene fusions and exert their tumorigenic action by two alternative mechanisms: overexpression of a gene in one of the breakpoints or the creation of a hybrid gene through the fusion of two genes, one in each breakpoint.
4. A total of 358 gene fusions, involving 337 different genes, are known at present and have been described in all the main subtypes of human neoplasia.
5. The prevalence of gene fusions varies considerably, from 0–100%, among different tumour types. Among malignant disorders, the proportions of gene fusion-positive cases are similar in haematological disorders, sarcomas and carcinomas.
6. The gene fusions identified to date account for approximately 20% of human cancer morbidity.
7. A number of conceptually important questions remain to be answered: why, how and when do chromosome aberrations originate? Are the resulting gene fusions sufficient for tumorigenesis, and if not, what is the pathogenetic relationship between these gene rearrangements and the other genetic and epigenetic alterations that characterize neoplastic cells?

要点翻译：

1. 染色体畸变是肿瘤的一个特征性表现，目前已在所有主要癌症类型中报道了超过5万例获得性染色体改变病例。
2. 复发性平衡染色体重排（尤其是易位）与特定肿瘤类型密切相关，并有充分证据表明它们是肿瘤发生过程中的起始事件。
3. 平衡染色体异常会导致基因融合的形成，并通过两种不同机制发挥其致瘤作用：断裂点中某个基因的过度表达，或通过两个断裂点中的基因融合形成杂交基因。
4. 目前已知有358种基因融合（涉及337个不同基因），这些融合在所有主要人类肿瘤亚型中均有描述。
5. 不同肿瘤类型中基因融合的发生率差异显著，从0%到100%不等。在恶性疾病中，血液系统疾病、肉瘤和癌中基因融合阳性病例的比例相近。
6. 迄今发现的基因融合约占人类癌症发病率的20%。
7. 仍有若干概念性重要问题有待解答：染色体畸变为何产生、如何产生以及何时产生？由此产生的基因融合是否足以导致肿瘤发生？若不足够，这些基因重排与肿瘤细胞特有的其他遗传和表观遗传改变之间存在怎样的致病关系？。

英文摘要：

Chromosome aberrations, in particular translocations and their corresponding gene fusions, have an important role in the initial steps of tumorigenesis; at present, 358 gene fusions involving 337 different genes have been identified. An increasing number of gene fusions are being recognized as important diagnostic and prognostic parameters in malignant haematological disorders and childhood sarcomas. The biological and clinical impact of gene fusions in the more common solid tumour types has been less appreciated. However, an analysis of available data shows that gene fusions occur in all malignancies, and that they account for 20% of human cancer morbidity. With the advent of new and powerful investigative tools that enable the detection of cytogenetically cryptic rearrangements, this proportion is likely to increase substantially.

摘要翻译： 

染色体畸变，尤其是易位及其相应的基因融合，在肿瘤发生的初始步骤中具有重要作用；目前，已发现涉及337个不同基因的358种基因融合。越来越多的基因融合被确认为恶性血液病和儿童肉瘤的重要诊断和预后参数。基因融合在更常见实体瘤类型中的生物学和临床影响尚未得到充分认识。然而，对现有数据的分析显示，基因融合存在于所有恶性肿瘤中，占人类癌症发病率的20%。随着能够检测细胞遗传学隐匿性重排的新型强大研究工具的出现，这一比例可能会显著增加。

原文链接：

The impact of translocations and gene fusions on cancer causation