title: Evidence for an unanticipated relationship between undifferentiated pleomorphic sarcoma and embryonal rhabdomyosarcoma.
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.
authors.affiliation: Department of Anatomic Pathology, Taussig Cancer Center and Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Rubin
authors.forename: Koichi
authors.initials: K
authors.lastname: Nishijo
authors.forename: Hung-I Harry
authors.initials: HI
authors.lastname: Chen
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Yi
authors.forename: David P
authors.initials: DP
authors.lastname: Schuetze
authors.forename: Ranadip
authors.initials: R
authors.lastname: Pal
authors.forename: Suresh I
authors.initials: SI
authors.lastname: Prajapati
authors.forename: Jinu
authors.initials: J
authors.lastname: Abraham
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Arenkiel
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Chen
authors.forename: Sean
authors.initials: S
authors.lastname: Davis
authors.forename: Amanda T
authors.initials: AT
authors.lastname: McCleish
authors.forename: Mario R
authors.initials: MR
authors.lastname: Capecchi
authors.forename: Joel E
authors.initials: JE
authors.lastname: Michalek
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Zarzabal
authors.forename: Javed
authors.initials: J
authors.lastname: Khan
authors.forename: Zhongxin
authors.initials: Z
authors.lastname: Yu
authors.forename: David M
authors.initials: DM
authors.lastname: Parham
authors.forename: Frederic G
authors.initials: FG
authors.lastname: Barr
authors.forename: Paul S
authors.initials: PS
authors.lastname: Meltzer
authors.forename: Yidong
authors.initials: Y
authors.lastname: Chen
authors.forename: Charles
authors.initials: C
authors.lastname: Keller
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D006801:Humans; D051379:Mice; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics; D018233:Rhabdomyosarcoma, Embryonal / Q000235:genetics / Q000473:pathology*; D012509:Sarcoma / Q000235:genetics / Q000473:pathology*
chemical_list: C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface