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.