Evidence for an Unanticipated Relationship between Undifferentiated Pleomorphic Sarcoma and Embryonal Rhabdomyosarcoma

Brian P. Rubin, Koichi Nishijo, Hung I.Harry Chen, Xiaolan Yi, David P. Schuetze, Ranadip Pal, Suresh I. Prajapati, Jinu Abraham, Benjamin R. Arenkiel, Qing Rong Chen, Sean Davis, Amanda T. McCleish, Mario R. Capecchi, Joel E. Michalek, Lee Ann Zarzabal, Javed Khan, Zhongxin Yu, David M. Parham, Frederic G. Barr, Paul S. MeltzerYidong Chen, Charles Keller

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Embryonal rhabdomyosarcoma (eRMS) shows the most myodifferentiation among sarcomas, yet the precise cell of origin remains undefined. Using Ptch1, p53 and/or Rb1 conditional mouse models and controlling prenatal or postnatal myogenic cell of origin, we demonstrate that eRMS and undifferentiated pleomorphic sarcoma (UPS) lie in a continuum, with satellite cells predisposed to giving rise to UPS. Conversely, p53 loss in maturing myoblasts gives rise to eRMS, which have the highest myodifferentiation potential. Regardless of origin, Rb1 loss modifies tumor phenotype to mimic UPS. In human sarcomas that lack pathognomic chromosomal translocations, p53 loss of function is prevalent, whereas Shh or Rb1 alterations likely act primarily as modifiers. Thus, sarcoma phenotype is strongly influenced by cell of origin and mutational profile.

Original languageEnglish (US)
Pages (from-to)177-191
Number of pages15
JournalCancer Cell
Volume19
Issue number2
DOIs
StatePublished - Feb 15 2011

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Rubin, B. P., Nishijo, K., Chen, H. I. H., Yi, X., Schuetze, D. P., Pal, R., Prajapati, S. I., Abraham, J., Arenkiel, B. R., Chen, Q. R., Davis, S., McCleish, A. T., Capecchi, M. R., Michalek, J. E., Zarzabal, L. A., Khan, J., Yu, Z., Parham, D. M., Barr, F. G., ... Keller, C. (2011). Evidence for an Unanticipated Relationship between Undifferentiated Pleomorphic Sarcoma and Embryonal Rhabdomyosarcoma. Cancer Cell, 19(2), 177-191. https://doi.org/10.1016/j.ccr.2010.12.023