Lineage of origin in rhabdomyosarcoma informs pharmacological response
| العنوان: | Lineage of origin in rhabdomyosarcoma informs pharmacological response |
|---|---|
| المؤلفون: | Simone Hettmer, Paul S. Meltzer, Benjamin Ehler, Lee Ann Zarzabal, Yaiza Núñez-Álvarez, Sheila T. Hampton, Elvira Carrió, Sean Davis, Mario R. Capecchi, Elaine T. Huang, Hung I Harry Chen, Charles Keller, Joel E. Michalek, Frank C. Marini, Amanda T. McCleish, Robin D. LeGallo, Robert L. Walker, Brian P. Rubin, Yi Chen, Jennifer Rebeles, Thomas A. Rando, Jinu Abraham, Amy J. Wagers, Suresh I. Prajapati, Martin Goros, Atiya Mansoor, Andrew S. Brack, Mònica Suelves, Christopher R. R. Bjornson, Hunter Wiebush, Koichi Nishijo, David M. Langenau |
| المصدر: | Genes & Development. 28:1578-1591 |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Pyridines, medicine.drug_class, Cell of origin, PAX3, Antineoplastic Agents, FOXO1, Biology, Epigenesis, Genetic, Mice, chemistry.chemical_compound, Cell Line, Tumor, Genetics, medicine, Transcriptional regulation, Animals, Humans, Paired Box Transcription Factors, Cell Lineage, Rhabdomyosarcoma, PAX3 Transcription Factor, Rhabdomyosarcoma, Alveolar, Forkhead Box Protein O1, Entinostat, Histone deacetylase inhibitor, Forkhead Transcription Factors, medicine.disease, Gene Expression Regulation, Neoplastic, Disease Models, Animal, chemistry, Benzamides, Cancer research, Alveolar rhabdomyosarcoma, Tumor Suppressor Protein p53, Research Paper, Developmental Biology |
| الوصف: | 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. |
| تدمد: | 1549-5477 0890-9369 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eeb74fceeee1bb771040e9134a16947e https://doi.org/10.1101/gad.238733.114 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....eeb74fceeee1bb771040e9134a16947e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15495477 08909369 |
|---|