Background

Mutation of the Duchenne muscular dystrophy (DMD) gene causes Duchenne and Becker muscular dystrophy, degenerative neuromuscular disorders that primarily affect voluntary muscles. However, increasing evidence implicates DMD in the development of all major cancer types. DMD is a large gene with 79 exons that codes for the essential muscle protein dystrophin. Alternative promotor usage drives the production of several additional dystrophin protein products with roles that extend beyond skeletal muscle. The importance and function(s) of these gene products outside of muscle are not well understood.

Conclusions

We highlight a clear role for DMD in the pathogenesis of several cancers, including sarcomas, leukaemia’s, lymphomas, nervous system tumours, melanomas and various carcinomas. We note that the normal balance of DMD gene products is often disrupted in cancer. The short dystrophin protein Dp71 is, for example, typically maintained in cancer whilst the full-length Dp427 gene product, a likely tumour suppressor, is frequently inactivated in cancer due to a recurrent loss of 5’ exons. Therefore, the ratio of short and long gene products may be important in tumorigenesis. In this review, we summarise the tumours in which DMD is implicated and provide a hypothesis for possible mechanisms of tumorigenesis, although the question of cause or effect may remain. We hope to stimulate further study into the potential role of DMD gene products in cancer and the development of novel therapeutics that target DMD.

中文翻译：

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杜氏肌营养不良症基因与癌症

背景

杜氏肌营养不良症 ( DMD)基因突变会导致杜氏肌营养不良症和贝克尔肌营养不良症，这是一种主要影响随意肌的退行性神经肌肉疾病。然而，越来越多的证据表明DMD与所有主要癌症类型的发展有关。DMD是一个具有 79 个外显子的大基因，编码必需的肌肉蛋白肌营养不良蛋白。替代启动子的使用可驱动几种额外的抗肌营养不良蛋白产品的产生，其作用超出骨骼肌范围。这些基因产物在肌肉之外的重要性和功能尚不清楚。

结论

我们强调DMD在多种癌症发病机制中的明确作用，包括肉瘤、白血病、淋巴瘤、神经系统肿瘤、黑色素瘤和各种癌症。我们注意到DMD基因产物的正常平衡在癌症中经常被破坏。例如，短抗肌营养不良蛋白 Dp71 通常在癌症中保留，而全长 Dp427 基因产物（一种可能的肿瘤抑制因子）在癌症中经常因 5' 外显子的反复丢失而失活。因此，短基因产物和长基因产物的比例可能在肿瘤发生中很重要。在这篇综述中，我们总结了与 DMD相关的肿瘤，并为肿瘤发生的可能机制提供了假设，尽管因果问题可能仍然存在。我们希望促进对DMD基因产物在癌症中的潜在作用的进一步研究，并开发针对DMD的新型疗法。