Lineage of origin in rhabdomyosarcoma informs pharmacological response
View/ Open
Author
Nunez-Alvarez, Y.
Carrio, E.
Chen, Hung-I Harry
Nishijo, K.
Huang, Elaine
Prajapati, Suresh I.
Walker, Robert L.
Davis, Sean
Rebeles, Jennifer
Wiebush, Hunter
McCleish, Amanda T.
Hampton, Sheila T.
Bjornson, Christopher R.R.
Rando, Thomas A.
Capecchi, Mario R.
Marini, Frank C.
Ehler, Benjamin R.
Zarzabal, Lee Ann
Goros, Martin W.
Michalek, Joel E.
Meltzer, Paul S.
LeGallo, Robin D.
Chen, Yidong
Suelves, Monica
Rubin, Brian P.
Keller, Charles
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1101/gad.238733.114Metadata
Show full item recordCitation
Abraham, J., Y. Nunez-Alvarez, S. Hettmer, E. Carrio, H.-I. H. Chen, K. Nishijo, E. T. Huang, et al. 2014. “Lineage of Origin in Rhabdomyosarcoma Informs Pharmacological Response.” Genes & Development 28 (14) (July 15): 1578–1591. doi:10.1101/gad.238733.114.Abstract
Lineage or cell of origin of cancers is often unknown and thus is not a consideration in therapeutic approaches. Alveolar rhabdomyosarcoma (aRMS) is an aggressive childhood cancer for which the cell of origin remains debated. We used conditional genetic mouse models of aRMS to activate the pathognomonic Pax3:Foxo1 fusion oncogene and inactivate p53 in several stages of prenatal and postnatal muscle development. We reveal that lineage of origin significantly influences tumor histomorphology and sensitivity to targeted therapeutics. Furthermore, we uncovered differential transcriptional regulation of the Pax3:Foxo1 locus by tumor lineage of origin, which led us to identify the histone deacetylase inhibitor entinostat as a pharmacological agent for the potential conversion of Pax3:Foxo1-positive aRMS to a state akin to fusion-negative RMS through direct transcriptional suppression of Pax3:Foxo1.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102765/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:25200507
Collections
- FAS Scholarly Articles [18295]
Contact administrator regarding this item (to report mistakes or request changes)