Wang Y.Marino-Enriquez A.Bennett R.R.Zhu M.Shen Y.Eilers G.JEN-CHIEH LEEHenze J.Fletcher B.S.Gu Z.Fox E.A.Antonescu C.R.Fletcher C.D.M.Guo X.Raut C.P.Demetri G.D.Van De Rijn M.Ordog T.Kunkel L.M.Fletcher J.A.2020-03-072020-03-0720141061-4036https://www.scopus.com/inward/record.uri?eid=2-s2.0-84901680208&doi=10.1038%2fng.2974&partnerID=40&md5=5f1a2de05b1cbdbecb48ecbf4c2944afhttps://scholars.lib.ntu.edu.tw/handle/123456789/473706Many 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. ? 2014 Nature America, Inc.[SDGs]SDG3dystrophin; anchorage independent growth; article; cell invasion; cell migration; clinical article; controlled study; embryonal rhabdomyosarcoma; female; fluorescence in situ hybridization; gastrointestinal stromal tumor; gene deletion; gene expression; gene inactivation; human; human cell; human tissue; leiomyosarcoma; male; multiplex ligation dependent probe amplification; muscular dystrophy; nucleotide sequence; priority journal; sarcoma cell; single nucleotide polymorphism; transcription initiation site; tumor suppressor gene; X chromosome; Animals; Cell Differentiation; Cell Line, Tumor; Cell Movement; Disease Progression; Dystrophin; Female; Gastrointestinal Stromal Tumors; Gene Deletion; Genes, Tumor Suppressor; Humans; In Situ Hybridization, Fluorescence; Interstitial Cells of Cajal; Leiomyosarcoma; Male; Mice; Mice, Inbred BALB C; Muscle Development; Muscle, Skeletal; Muscular Dystrophies; Neoplasm Invasiveness; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Rhabdomyosarcoma; Sarcomajournal article10.1038/ng.2974247931342-s2.0-84901680208