Data from Credentialing a Preclinical Mouse Model of Alveolar Rhabdomyosarcoma
Year: 2023
Type: other
Abstract: The highly aggressive muscle cancer alveolar rhabdomyosarcoma (ARMS) is one of the most common soft tissue sarcoma of childhood, yet the outcome for the unresectable and metastatic disease is dismal and unchanged for nearly three decades. To better understand the pathogenesis of this disease and to facilitate novel preclinical approaches, we previously developed a conditional mouse model of ARMS by faithfully recapitulating the genetic mutations observed in the human disease, i.e., activation of Pax3:Fkhr fusion gene with either p53 or Cdkn2a inactivation. In this report, we show that this model recapitulates the immunohistochemical profile and the rapid progression of the human disease. We show that Pax3:Fkhr expression increases during late preneoplasia but tumor cells undergoing metastasis are under apparent selection for Pax3:Fkhr expression. At a whole-genome level, a cross-species gene set enrichment analysis and metagene projection study showed that our mouse model is most similar to human ARMS when compared with other pediatric cancers. We have defined an expression profile conserved between mouse and human ARMS, as well as a Pax3:Fkhr signature, including the target gene, SKP2. We further identified 7 “druggable” kinases overexpressed across species. The data affirm the accuracy of this genetically engineered mouse model. [Cancer Res 2009;69(7):2902–11]
Authors: Koichi Nishijo, Qing-Rong Chen, Lei Zhang, Amanda T. McCleish, Andrea Rodriguez, Min Jung Cho, Suresh I. Prajapati, Jonathan A.L. Gelfond, Gary B. Chisholm, Joel E. Michalek, Bruce J. Aronow, Frederic G. Barr, R. Lor Randall, Marc Ladanyi, Stephen J. Qualman, Brian P. Rubin, Robin D. LeGallo, Chiayeng Wang, Javed Khan, Charles Keller
Institutions: National Cancer Institute, Science Applications International Corporation (United States), University of Illinois Chicago, University of Cincinnati, University of Pennsylvania, University of Utah, Memorial Sloan Kettering Cancer Center, Nationwide Children's Hospital, Cleveland Clinic, The University of Texas at San Antonio Health Science Center, Pediatrics and Genetics
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4361822335