Studying Mechanisms of Radiation Therapy Resistance in Samples From Younger Patients With Rhabdomyosarcoma
RATIONALE: Studying samples of tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors find better ways to treat cancer.
PURPOSE: This laboratory study is looking into mechanisms of radiation therapy resistance in samples from younger patients with rhabdomyosarcoma.
Genetic: DNA methylation analysis
Genetic: RNA analysis
Genetic: fluorescence in situ hybridization
Genetic: gene expression analysis
Genetic: microarray analysis
Genetic: polymorphism analysis
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
|Official Title:||Identifying and Validating Novel Mechanisms of Radiation Resistance in Rhabdomyosarcoma|
- Molecular response/resistance signatures of radiotherapy and standard chemoradiation using Spearman's rho [ Designated as safety issue: No ]
- Novel pathway/biomarkers associated with clinical response [ Designated as safety issue: No ]
- Novel pathway/biomarkers associated with local control rates using log-rank and univariate/multivariate Cox regression analysis [ Designated as safety issue: No ]
- Novel pathway/biomarkers associated with overall survival rates using log-rank and univariate/multivariate Cox regression analysis [ Designated as safety issue: No ]
|Study Start Date:||June 2012|
|Estimated Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
- Determine the molecular response/resistance signatures with radiotherapy and standard chemoradiation treatments using the xenograft model of the Pediatric Preclinical Testing Program (PPTP).
- Validate these novel pathways/biomarkers by their detection within clinically annotated patient tumor tissue samples and testing their associations with clinical response, local control rates, and overall survival rates.
OUTLINE: Archived tissue samples of matched primary-relapsed and non-matched primary are analyzed for genomic DNA, DNA methylation profiles, RNA sequencing, differences between alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS), gene expression profiles, target-of-rapamycin complex 1 (TORC1) and TORC2 pathway intermediates, and paired box 3 (PAX3)/forkhead box O1 (FOXO1) translocation by microarray, immunohistochemical staining, and fluorescence in situ hybridization (FISH).
|Principal Investigator:||Christopher E. Pelloski, MD||Ohio State University Comprehensive Cancer Center|