Biomarkers in Young Patients With Neuroblastoma
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.
|Neuroblastoma||Genetic: DNA analysis Genetic: DNA methylation analysis Genetic: RNA analysis Genetic: comparative genomic hybridization Genetic: mutation analysis Genetic: polymorphism analysis|
|Study Design:||Observational Model: Case-Only
Time Perspective: Retrospective
|Official Title:||Therapeutically Applicable Research to Generate Effective Treatments (TARGET) for Neuroblastoma|
- Discovery of therapeutically relevant driver mutations
- Identification of a set of neuroblastoma specimens for analyses
- Genome-wide DNA copy number and allelic status
- Genome-wide methylation profile
- Genome-wide microRNA expression profile
- Genome-wide RNA expression signatures
- Identification of mutations in candidate therapeutic targets
- Characterization of the relapsed high-risk neuroblastoma genome and epigenome
|Study Start Date:||July 2010|
|Study Completion Date:||May 2016|
|Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
- To discover the therapeutically relevant driver mutations in high-risk pediatric neuroblastoma.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01169376
|Principal Investigator:||John M. Maris, MD||Children's Hospital of Philadelphia|