Neuroblastoma
Conditions
Keywords
disseminated neuroblastoma, localized resectable neuroblastoma, localized unresectable neuroblastoma, regional neuroblastoma, stage 4S neuroblastoma
Brief summary
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
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.
Interventions
GENETICDNA analysis
GENETICDNA methylation analysis
GENETICRNA analysis
GENETICcomparative genomic hybridization
GENETICmutation analysis
GENETICpolymorphism analysis
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Observational model
CASE_ONLY
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 30 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Discovery of therapeutically relevant driver mutations | — |
Secondary
| Measure | Time frame |
|---|---|
| Genome-wide DNA copy number and allelic status | — |
| Genome-wide methylation profile | — |
| Genome-wide microRNA expression profile | — |
| Identification of a set of neuroblastoma specimens for analyses | — |
| Identification of mutations in candidate therapeutic targets | — |
| Characterization of the relapsed high-risk neuroblastoma genome and epigenome | — |
| Genome-wide RNA expression signatures | — |
Outcome results
None listed