Cancer Cell: Evidence for an Unanticipated Relationship between Undifferentiated Pleomorphic Sarcoma and Embryonal Rhabdomyosarcoma
Brian P.Rubin1, KoichiNishijo2, Hung-I HarryChen2, XiaolanYi2, David P.Schuetze1, RanadipPal3, Suresh I.Prajapati2, JinuAbraham2, Benjamin R.Arenkiel4, Qing-RongChen5, SeanDavis6, Amanda T.McCleish2, Mario R.Capecchi7, Joel E.Michalek8, Lee AnnZarzabal8, JavedKhan5, ZhongxinYu9, David M.Parham9, CharlesKeller2111213
Summary
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 has 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, the sarcoma phenotype is strongly influenced by a cell of origin and mutational profile.
Since 2004, UT Health San Antonio, Greehey Children’s Cancer Research Institute’s (Greehey CCRI) mission has been to advance scientific knowledge relevant to childhood cancer, contribute to understanding its causes, and accelerate the translation of knowledge into novel therapies. Greehey CCRI strives to have a national and global impact on childhood cancer by discovering, developing, and disseminating new scientific knowledge. Our mission consists of three key areas — research, clinical, and education.
Stay connected with the Greehey CCRI on Facebook, Twitter, LinkedIn, and Instagram.