biomarkers in young patients with neuroblastoma

Conditions: Neuroblastoma

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.

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.

Eligibility 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

Keywords: disseminated neuroblastoma localized resectable neuroblastoma localized unresectable neuroblastoma regional neuroblastoma stage 4s neuroblastoma