Studying Mechanisms of Radiation Therapy Resistance in Samples From Younger Patients With Rhabdomyosarcoma

Observational Study Model: Cohort Time Perspective: Retrospective Biospecimen Retention: Samples with DNA Biospecimen Description: Tissue Study Population Description: Primary care clinic Sampling Method: Non-probability sample

OBJECTIVES:

I. Determine the molecular response/resistance signatures with radiotherapy and standard chemoradiation treatments using the xenograft model of the Pediatric Preclinical Testing Program (PPTP).

II. 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).

Inclusion criteria

• Tissues requested from the Children Oncology Group (COG) sarcoma banking protocol COG-D9902
• All subtypes of rhabdomyosarcoma specimens

• Matched primary-relapsed specimens (from same patient, separated by time):

• Frozen tissue if available
• Scrolls of formalin-fixed paraffin-embedded tissue (if frozen not available)
• 10 unstained formalin-fixed paraffin-embedded thin sections
• All other general (primary or relapsed) cases

• 10 unstained formalin-fixed paraffin-embedded thin sections