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

Study Overview
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Brief Summary
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This laboratory study is looking into mechanisms of radiation therapy resistance in samples from younger patients with rhabdomyosarcoma. 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

Detailed Description
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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).

Official Title
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Observational - Identifying and Validating Novel Mechanisms of Radiation Resistance in Rhabdomyosarcoma

Conditions
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Alveolar Childhood Rhabdomyosarcoma, Embryonal Childhood Rhabdomyosarcoma, Previously Treated Childhood Rhabdomyosarcoma, Previously Untreated Childhood Rhabdomyosarcoma, Recurrent Childhood Rhabdomyosarcoma

Intervention / Treatment
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* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Correlative (laboratory biomarker analysis)<br>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). | Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular response |  | Up to 1 year | 
| Novel pathway/biomarkers detected within clinically annotated patient tumor tissue samples |  | Up to 1 year |