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Dystrophin is a tumor suppressor in human cancers with myogenic programs. Nature genetics Wang, Y., Marino-Enriquez, A., Bennett, R. R., Zhu, M., Shen, Y., Eilers, G., Lee, J., Henze, J., Fletcher, B. S., Gu, Z., Fox, E. A., Antonescu, C. R., Fletcher, C. D., Guo, X., Raut, C. P., Demetri, G. D., van de Rijn, M., Ordog, T., Kunkel, L. M., Fletcher, J. A. 2014; 46 (6): 601-606

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.

View details for DOI 10.1038/ng.2974

View details for PubMedID 24793134