Dystrophin is a tumor suppressor in human cancers with myogenic programs Journal Article
| Authors: | Wang, Y.; Marino-Enriquez, A.; Bennett, R. R.; Zhu, M.; Shen, Y.; Eilers, G.; Lee, J. C.; Henze, 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. |
| Article Title: | Dystrophin is a tumor suppressor in human cancers with myogenic programs |
| 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. © 2014 Nature America, Inc. |
| Keywords: | clinical article; controlled study; human tissue; human cell; single nucleotide polymorphism; gene deletion; gastrointestinal stromal tumor; gene expression; tumor suppressor gene; fluorescence in situ hybridization; nucleotide sequence; cell migration; x chromosome; gene inactivation; leiomyosarcoma; anchorage independent growth; cell invasion; embryonal rhabdomyosarcoma; transcription initiation site; dystrophin; sarcoma cell; multiplex ligation dependent probe amplification; human; male; female; priority journal; article; muscular dystrophy |
| Journal Title: | Nature Genetics |
| Volume: | 46 |
| Issue: | 6 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2014-06-01 |
| Start Page: | 601 |
| End Page: | 606 |
| Language: | English |
| DOI: | 10.1038/ng.2974 |
| PROVIDER: | scopus |
| PUBMED: | 24793134 |
| PMCID: | PMC4225780 |
| DOI/URL: | |
| Notes: | Nat. Genet. -- Export Date: 8 July 2014 -- CODEN: NGENE -- Molecular Sequence Numbers: GENBANK: GSE53021; -- Source: Scopus |
