The Duchenne muscular dystrophy gene and cancer
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REVIEW
The Duchenne muscular dystrophy gene and cancer Leanne Jones 1 & Michael Naidoo 1 & Lee R. Machado 1,2 & Karen Anthony 1 Accepted: 23 October 2020 # The Author(s) 2020
Abstract 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. Keywords Duchenne muscular dystrophy . DMD . Dp71 . Dystrophin . Cancer
1 Introduction The Duchenne muscular dystrophy gene (DMD) is best known for its role in the disease of the same name [1]. DMD encodes dystrophin protein (Dp) products which are named based on their length in kDa. The major, and full-length, product is the 427 kDa dystrophin protein (Dp427) predominantly expressed in skeletal muscle [1]. Dp427 is essential for maintaining muscle integrity through connecting the actin cytoskeleton to the extracellular matrix. It achieves this through association with various proteins to form a transmembrane scaffolding complex called the dystrophin-associated protein Leanne Jones and Michael Naidoo share first authorship. Lee R. Machado and Karen Anthony share senior authorship. * Karen Anthony [email protected] 1
Centre for Physical Activity and Life Sciences, University of Northampton, University Drive, Northampton NN1 5PH, UK
2
Department of Genetics and Genome Science, University of Leicester, LE1 7RH Leicester, UK
complex (DAPC). The loss of dystrophin, through out-offrame DMD gene mutation, in Duchenne patients is responsible for severe muscle degeneration and premature death [1]. The DMD gene consists of 79 exons. It is one of the largest human genes and is located on the short arm of the X chromoso
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