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