Dux transcription factors define a molecular subtype of cancer originating from adult stem cells

Using skeletal muscle regeneration as a paradigm, we show that regeneration induced activation of p53 deficient adult stem cells is required to promote tumor formation. Purification of lineage-traced tumor cells enabled unambiguous identification of distinct oncogenic copy number amplifications (CNA). In a subset of tumors we identified a novel CNA of Duxbl, a homolog of human homeobox transcription factor Dux4 which defines cleavage stage-specific transcriptional programs of totipotent ES cells.