Biomarkers in Young Patients With Neuroblastoma

Study Overview
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Brief Summary
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RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer. PURPOSE: This research study is studying biomarkers in young patients with neuroblastoma.

Detailed Description
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OBJECTIVES: Primary To discover the therapeutically relevant driver mutations in high-risk pediatric neuroblastoma. Secondary To identify a set of highly annotated neuroblastoma specimens (primary tumors and cell lines) for comprehensive genomic analyses, validation studies, resequencing efforts, and future functional assays. To define genome-wide DNA copy number and allelic status in at least 300 high-risk and 50 low-risk neuroblastoma primary untreated tumors, and 30 human neuroblastoma-derived cell lines. To define the genome-wide methylation profile of neuroblastoma in a minimum of 200 high-risk cases. To define the genome-wide microRNA expression profile of neuroblastoma in a minimum of 200 high-risk cases. To define genome-wide RNA expression signatures, including splice variations, in the same tumors and cell lines studied above. To identify mutations in candidate therapeutic targets using a staged resequencing strategy with ultimate genome-scale next generation resequencing of 3 genomes for 200 high-risk cases: the neuroblastoma genome and transcriptome as well as the paired constitutional genome. To characterize the relapsed high-risk neuroblastoma genome and epigenome. OUTLINE: This is a multicenter study. Previously collected samples are analyzed to define the genome-wide DNA copy number and allelic status; to define the genome-wide methylation profile of high-risk neuroblastoma cases; to define the genome-wide microRNA expression profile of high-risk neuroblastoma cases; to define the genome-wide RNA expression and relating gene expression to DNA copy number and gene polymorphisms, DNA methylation, and microRNA expression; to resequence three genomes: the neuroblastoma genome, the transcriptome, and the paired constitutional genome; and to characterize the relapsed high-risk neuroblastoma genome and epigenome. PROJECTED ACCRUAL: A total of 300 tumor samples from patients with high-risk disease, 50 tumor samples from patients with low-risk primary neuroblastoma, and 30 human neuroblastoma-derived cell lines will be accrued for this study.

Official Title
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Therapeutically Applicable Research to Generate Effective Treatments (TARGET) for Neuroblastoma

Conditions
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Neuroblastoma

Intervention / Treatment
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* Genetic: DNA analysis
* Genetic: DNA methylation analysis
* Genetic: RNA analysis
* Genetic: comparative genomic hybridization
* Genetic: mutation analysis
* Genetic: polymorphism analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Registered on the COG-ANBL00B1 Neuroblastoma Biology Study or its CCG or POG precursor Sufficient high-quality tumor material available for the proposed studies meeting the following criteria: Tissue histopathologic review with > 70% tumor cells in sections adjacent to areas used for nucleic acid preparation Matched normal cells (blood or uninvolved bone marrow) available ≥ 5 μg DNA available ≥ 5 μg RNA available ≥ 200 mg tissue available Tumor samples must meet 1 of the following criteria: High-risk tumor With or without MYCN amplification With or without tumor progression or relapse (during ≥ 2.5 years of follow up) Patients aged 18 months to 5 years Low-risk tumor Primary neuroblastoma Stage I disease (completely resected) No event in ≥ 3 years of follow up Cell lines representing diverse high-risk genetics including with or without MYCN amplification and clinical course (at diagnosis or after relapse) PATIENT CHARACTERISTICS: Not specified PRIOR CONCURRENT THERAPY: Not specified

Ages Eligible for Study
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Maximum Age: 30 Years

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

| Intervention/Treatment |
| --- |
|Genetic: DNA analysis|nan|
|Genetic: DNA methylation analysis|nan|
|Genetic: RNA analysis|nan|
|Genetic: comparative genomic hybridization|nan|
|Genetic: mutation analysis|nan|
|Genetic: polymorphism analysis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Discovery of therapeutically relevant driver mutations |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of a set of neuroblastoma specimens for analyses |  |  | 
| Genome-wide DNA copy number and allelic status |  |  | 
| Genome-wide methylation profile |  |  | 
| Genome-wide microRNA expression profile |  |  | 
| Genome-wide RNA expression signatures |  |  | 
| Identification of mutations in candidate therapeutic targets |  |  | 
| Characterization of the relapsed high-risk neuroblastoma genome and epigenome |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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disseminated neuroblastoma, localized resectable neuroblastoma, localized unresectable neuroblastoma, regional neuroblastoma, stage 4S neuroblastoma