title: Modeling clear cell sarcomagenesis in the mouse: cell of origin differentiation state impacts tumor characteristics.
abstract: Clear cell sarcoma (CCS) of tendons and aponeuroses is a deadly soft-tissue malignancy resembling melanoma, with a predilection for young adults. EWS-ATF1, the fusion product of a balanced chromosomal translocation between chromosomes 22 and 12, is considered the definitional feature of the tumor. Conditional expression of the EWS-ATF1 human cDNA in the mouse generates CCS-like tumors with 100% penetrance. Tumors, developed through varied means of initiating expression of the fusion oncogene, model human CCS morphologically, immunohistochemically, and by genome-wide expression profiling. We also demonstrate that although fusion oncogene expression in later stages of differentiation can transform mesenchymal progenitor cells and generate tumors resembling CCS generally, expression in cells retaining stem cell markers permits the full melanoma-related phenotype.
authors: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors: Krystal M
authors: KM
authors: Straessler
authors: Kevin B
authors: KB
authors: Jones
authors: Hao
authors: H
authors: Hu
authors: Huifeng
authors: H
authors: Jin
authors: Matt
authors: M
authors: van de Rijn
authors: Mario R
authors: MR
authors: Capecchi
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018227:Sarcoma, Clear Cell / Q000235:genetics / Q000473:pathology*; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C111598:EWS-ATF1 fusion protein, human; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D014157:Transcription Factors