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The identity of tumor-initiating cells in many cancer types is unknown. Tumors often express genes associated with embryonic development, although the contributions of zygotic programs to tumor initiation and formation are poorly understood. Here, we show that regeneration-induced loss of quiescence in p53-deficient muscle stem cells (MuSCs) results in rhabdomyosarcoma formation with 100% penetrance. Genomic analyses of purified tumor cells revealed spontaneous and discrete oncogenic amplifications in MuSCs that drive tumorigenesis, including, but not limited to, the amplification of the cleavage-stage Dux transcription factor (TF) Duxbl. We further found that Dux factors drive an early embryonic gene signature that defines a molecular subtype across a broad range of human cancers. Duxbl initiates tumorigenesis by enforcing a mesenchymal-to-epithelial transition, and targeted inactivation of Duxbl specifically in Duxbl-expressing tumor cells abolishes their expansion. These findings reveal how regeneration and genomic instability can interact to activate zygotic genes that drive tumor initiation and growth.
Pubmed ID: 30449715 RIS Download
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View all literature mentionsJava toolset for working with next generation sequencing data in the BAM format.
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View all literature mentionsThis monoclonal targets myosin, sarcomere (MHC)
View all literature mentionsThis monoclonal targets Myogenin
View all literature mentionsThis polyclonal targets MYOG
View all literature mentionsThis unknown targets Recombinant mouse p53 protein
View all literature mentionsThis monoclonal targets V5 Tag
View all literature mentionsThis polyclonal targets V5 tag - ChIP Grade
View all literature mentionsThis monoclonal targets Human Myogenic Factor 3 (MYOD1)
View all literature mentionsThis polyclonal targets MYOD1
View all literature mentionsThis polyclonal targets 53BP1 antibody
View all literature mentionsThis unknown targets ATM / ATR Substrate, phospho (Ser / Thr)
View all literature mentionsThis polyclonal targets Histone H2A.X
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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