Therapeutically Applicable Research to Generate Effective Treatments (TARGET) for Neuroblastoma
- To discover the therapeutically relevant driver mutations in high-risk pediatric
- 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
- To define the genome-wide methylation profile of neuroblastoma in a minimum of 200
- 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
- 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.
Discovery of therapeutically relevant driver mutations
John M. Maris, MD
Children's Hospital of Philadelphia
United States: Federal Government