Biomarkers in Young Patients With Neuroblastoma

Overview

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.

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