Dystrophin is a tumor suppressor in human cancers with myogenic programs

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Abstract

Many common human mesenchymal tumors, including gastrointestinal stromal tumor (GIST), rhabdomyosarcoma (RMS) and leiomyosarcoma (LMS), feature myogenic differentiation. Here we report that intragenic deletion of the dystrophin-encoding and muscular dystrophy-associated DMD gene is a frequent mechanism by which myogenic tumors progress to high-grade, lethal sarcomas. Dystrophin is expressed in the non-neoplastic and benign counterparts of GIST, RMS and LMS tumors, and DMD deletions inactivate larger dystrophin isoforms, including 427-kDa dystrophin, while preserving the expression of an essential 71-kDa isoform. Dystrophin inhibits myogenic sarcoma cell migration, invasion, anchorage independence and invadopodia formation, and dystrophin inactivation was found in 96%, 100% and 62% of metastatic GIST, embryonal RMS and LMS samples, respectively. These findings validate dystrophin as a tumor suppressor and likely anti-metastatic factor, suggesting that therapies in development for muscular dystrophies may also have relevance in the treatment of cancer.

Original languageEnglish (US)
Pages (from-to)601-606
Number of pages6
JournalNature Genetics
Volume46
Issue number6
DOIs
Publication statusPublished - Jun 2014

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ASJC Scopus subject areas

  • Genetics

Cite this

Wang, Y., Marino-Enriquez, A., Bennett, R. R., Zhu, M., Shen, Y., Eilers, G., ... Fletcher, J. A. (2014). Dystrophin is a tumor suppressor in human cancers with myogenic programs. Nature Genetics, 46(6), 601-606. https://doi.org/10.1038/ng.2974