TY - JOUR
T1 - Evidence for an Unanticipated Relationship between Undifferentiated Pleomorphic Sarcoma and Embryonal Rhabdomyosarcoma
AU - Rubin, Brian P.
AU - Nishijo, Koichi
AU - Chen, Hung I.Harry
AU - Yi, Xiaolan
AU - Schuetze, David P.
AU - Pal, Ranadip
AU - Prajapati, Suresh I.
AU - Abraham, Jinu
AU - Arenkiel, Benjamin R.
AU - Chen, Qing Rong
AU - Davis, Sean
AU - McCleish, Amanda T.
AU - Capecchi, Mario R.
AU - Michalek, Joel E.
AU - Zarzabal, Lee Ann
AU - Khan, Javed
AU - Yu, Zhongxin
AU - Parham, David M.
AU - Barr, Frederic G.
AU - Meltzer, Paul S.
AU - Chen, Yidong
AU - Keller, Charles
N1 - Funding Information:
Trainee and research support was provided by the Scott Carter Foundation as well K99NS064171-02 and 5R01CA133229-04. Human tissue samples were provided by the NCI-supported Cooperative Human Tissue Network. The NICHD-supported DSHB is maintained by The University of Iowa. Authors thank Maricela Castillo for technical assistance.
PY - 2011/2/15
Y1 - 2011/2/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79751484162&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2010.12.023
DO - 10.1016/j.ccr.2010.12.023
M3 - Article
C2 - 21316601
AN - SCOPUS:79751484162
VL - 19
SP - 177
EP - 191
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 2
ER -