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Study of Tumor Recurrence Related to the Expression of the PAX3-FOXO1 Oncogenic Transcription Factor in Fusion-Positive Rhabdomyosarcoma
dbGaP
Data Resource:  dbGaP
Point of Contact:  
Frederic G. Barr, MD, PhD,  
Project

About This Dataset
Alveolar rhabdomyosarcoma (ARMS) is a highly aggressive pediatric soft tissue cancer characterized by a recurrent 2;13 chromosome translocation. This translocation generates a PAX3-FOXO1 (P3F) fusion gene, which encodes a chimeric transcription factor with oncogenic activity. Using a human myoblast system that models targeted therapy directed against P3F, we demonstrated that the expression of the fibroblast growth factor 8 (FGF8), a direct transcriptional target of P3F, is necessary and sufficient for PAX3-FOXO1-independent tumor recurrence in addition to be required for the tumorigenic activity of primary tumors expressing P3F. In addition, we showed that FGF8 is expressed in human rhabdomyosarcoma cell lines that express P3F. We also demonstrated that FGF8 contributes to their proliferation and transformation in vitro, and is sufficient to maintain their oncogenicity after the loss of P3F expression. We suggest that targeting the expression of the PAX3-FOXO1 transcription factor can generate resistance and recommend that additional anticipated therapeutic approaches, such as targeting FGF8 pathway, may avoid this resistance mechanism.
Core Data Elements
Number of Cases
17
Case Sex
Not Reported (17)
Case Age At Diagnosis
Pediatric and Young Adult (<40 years) (17)
Case Race
Not Reported (17)
Case Ethnicity
Not Reported (17)
Case Disease Diagnosis
Rhabdomyosarcoma (17)
Case Tumor Site
Not Reported (17)
Additional Data Elements
DBGAP STUDY IDENTIFIER
Charts
Not Reported (17)
17Not Reported