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. Meltzer; Yidong Chen; Charles Keller

doi:10.1016/j.ccr.2010.12.023

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

Electrical and Computer Engineering

Research output: Contribution to journal › Article › peer-review

119 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 language	English
Pages (from-to)	177-191
Number of pages	15
Journal	Cancer Cell
Volume	19
Issue number	2
DOIs	https://doi.org/10.1016/j.ccr.2010.12.023
State	Published - Feb 15 2011

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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

Rubin, Brian P. ; Nishijo, Koichi ; Chen, Hung I.Harry ; Yi, Xiaolan ; Schuetze, David P. ; Pal, Ranadip ; Prajapati, Suresh I. ; Abraham, Jinu ; Arenkiel, Benjamin R. ; Chen, Qing Rong ; Davis, Sean ; McCleish, Amanda T. ; Capecchi, Mario R. ; Michalek, Joel E. ; Zarzabal, Lee Ann ; Khan, Javed ; Yu, Zhongxin ; Parham, David M. ; Barr, Frederic G. ; Meltzer, Paul S. ; Chen, Yidong ; Keller, Charles. / Evidence for an Unanticipated Relationship between Undifferentiated Pleomorphic Sarcoma and Embryonal Rhabdomyosarcoma. In: Cancer Cell. 2011 ; Vol. 19, No. 2. pp. 177-191.

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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.",

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

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doi = "10.1016/j.ccr.2010.12.023",

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Rubin, BP, Nishijo, K, Chen, HIH, Yi, X, Schuetze, DP, Pal, R, Prajapati, SI, Abraham, J, Arenkiel, BR, Chen, QR, Davis, S, McCleish, AT, Capecchi, MR, Michalek, JE, Zarzabal, LA, Khan, J, Yu, Z, Parham, DM, Barr, FG, Meltzer, PS, Chen, Y & Keller, C 2011, 'Evidence for an Unanticipated Relationship between Undifferentiated Pleomorphic Sarcoma and Embryonal Rhabdomyosarcoma', Cancer Cell, vol. 19, no. 2, pp. 177-191. https://doi.org/10.1016/j.ccr.2010.12.023

Evidence for an Unanticipated Relationship between Undifferentiated Pleomorphic Sarcoma and Embryonal Rhabdomyosarcoma. / Rubin, Brian P.; Nishijo, Koichi; Chen, Hung I.Harry; Yi, Xiaolan; Schuetze, David P.; Pal, Ranadip; Prajapati, Suresh I.; Abraham, Jinu; Arenkiel, Benjamin R.; Chen, Qing Rong; Davis, Sean; McCleish, Amanda T.; Capecchi, Mario R.; Michalek, Joel E.; Zarzabal, Lee Ann; Khan, Javed; Yu, Zhongxin; Parham, David M.; Barr, Frederic G.; Meltzer, Paul S.; Chen, Yidong; Keller, Charles.

In: Cancer Cell, Vol. 19, No. 2, 15.02.2011, p. 177-191.

Research output: Contribution to journal › Article › peer-review

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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

PY - 2011/2/15

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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.

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