Neuroblastoma

Neuroblastoma (NBL) is a cancer that arises in immature nerve cells of the sympathetic nervous system and affects mostly infants and children. Neuroblastoma accounts for ~12% of childhood cancer mortality, with those between 18 months and 5 years of age being most severely impacted. Identifying genomic alterations in high risk (HR) NBL cases and further targeting those lesions therapeutically would offer a chance at improved survival outcomes for these patients with poor prognosis. In addition, current NBL treatment includes harsh chemoradiotherapies that generally leave surviving children with lifelong side effects. The discovery of novel therapeutic targets in neuroblastoma could reduce the burden of sustained complications for patients who are fortunate enough to conquer the disease.

TARGET NBL Project

Neuroblastoma was chosen as the second disease to be studied in the TARGET initiative, following the success of the TARGET ALL pilot project. The NBL project team employed similar comprehensive genomic approaches to identify new therapeutic targets for pediatric HR NBL. Data were generated using clinically annotated, matched tumor and normal samples obtained from patients enrolled in various Children's Oncology Group (COG) biology and clinical trials. Additional funding, largely through the American Recovery and Reinvestment Act (ARRA) of 2009, made it possible to expand the NBL pilot project to include additional molecular characterization and sequencing for this large cohort of cases.

Genome-wide analysis

• Gene expression (Affymetrix Human Exon 1.0 ST v2 platform)
• Copy number analyses, paired tumor & normal (Illumina 550K SNP arrays)
• Targeted Sequencing (Sanger)
  • 117 selected genes
• 2nd and 3rd Generation Sequencing
  • Whole Genome Sequencing
  • Whole Exome Sequencing
  • Transcriptome Sequencing

The types of data on 582 clinically annotated patient cases

• 100 – 200 fully characterized (gene expression, copy number analysis, and sequencing)
• 300+ partially characterized

Data generated for this project will be made available to the research community through the TARGET Data Matrix rapidly upon completion of validation.

Investigators

The TARGET NBL project team consists of COG investigators at various institutions who work together with the scientists, analysts, project managers and technicians from the COG (Biorepository, Data and Statistics Core) and NCI offices (Office of Cancer Genomics, Clinical Therapy Evaluation Program, Center for Cancer Research and Center for Bioinformatics and Information Technology). This collaborative network is led by the following:

Principal Investigator – Children's Hospital of Philadelphia

• John M. Maris, MD.

Co-Principal Investigator – Children's Hospital of Los Angeles

• Robert Seeger, MD.

NCI Intramural Lead Investigator – National Cancer Institute, Center for Cancer Research

• Javed Khan, MD.