The genetic landscape of high-risk neuroblastoma

Nat Genet. Volume 45, Issue 3 p.279-284, 20 January 2013 10.1038/ng.2529

Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 affected individuals (cases) using a combination of whole-exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per Mb (0.48 nonsilent) and notably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, and an additional 7.1% had focal deletions), MYCN (1.7%, causing a recurrent p.Pro44Leu alteration) and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1 and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies that rely on frequently altered oncogenic drivers.

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Supplemental Data

• GDC Manifests
  • Controlled-Access Data Download Manifest (11 Files)
  • Open-Access Data Download Manifest (23 Files)
  • WGS CGI Files Download Manifest (137 Files)

• Copy Number Array
  • TARGET NBL Copy number array Level 1 Data (Controlled)
  • TARGET NBL Copy number array Level 2 Data (Controlled)
  • TARGET NBL Copy number array Level 3 Data
  • TARGET NBL Copy number array Design Information
  • TARGET NBL Copy number array Metadata
• Gene Expression Array
  • TARGET NBL Gene expression array Level 1 Data (Controlled)
  • TARGET NBL Gene expression array Level 2 Data (Controlled)
  • TARGET NBL Gene expression array Level 3 Data
  • TARGET NBL Gene expression array Metadata
• mRNA-Seq
  • TARGET NBL RNA-seq Level 3 data
  • TARGET NBL RNA-seq Level 3 data (Controlled)
  • TARGET NBL RNA-seq Metadata
• miRNA-Seq
  • TARGET NBL miRNA-seq Level 3 Data
  • TARGET NBL miRNA-seq Metadata
• Whole Exome Sequencing
  • TARGET NBL WXS Level 3 Data
  • TARGET NBL WXS Level 3 Data (Controlled)
  • TARGET NBL WXS Metadata
• Methylation Array
  • TARGET NBL Methylation array Level 1 Data (Controlled)
  • TARGET NBL Methylation array Level 2 Data
  • TARGET NBL Methylation array Level 3 Data
  • TARGET NBL Methylation array Metadata
• Whole Genome Sequencing
  • TARGET NBL WGS Level 3 Data
  • TARGET NBL WGS Level 3 Data (Controlled)
  • TARGET NBL WGS Level 4 Data
  • TARGET NBL WGS Metadata
• Targeted Capture Sequencing
  • TARGET NBL Targeted Capture Sequencing Level 3 Data
  • TARGET NBL Targeted Capture Sequencing Level 3 Data (Controlled)
  • TARGET NBL Targeted Capture Sequencing Design
  • TARGET NBL Targeted Capture Sequencing Metadata
• GWAS
  • TARGET NBL GWAS Level 2 Data (Controlled)
• Miscellaneous Files
  • TARGET NBL Sample Matrices
  • TARGET NBL ID Mapping Information
  • TARGET NBL CGI Requested Reports (Controlled)

Additional Resources

• OCG TARGET Data Matrix (link is external) Office of Cancer Genomics
• TARGET-NBL at SRA (link is external) NCBI

Instructions for Data Download

Open Access Data

1. Download the appropriate manifest file from the publication page
2. Use the manifest file to download data using the GDC Data Transfer Tool (DTT) or the GDC API
   • GDC DTT ( Download, User's Guide)
   • GDC API ( User’s Guide)

Controlled Access Data

1. Download the appropriate manifest file from the publication page
2. Download a token from the GDC Data Portal
   • GDC Data Portal ( Launch, User’s Guide)
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   • GDC DTT ( Download, User’s Guide)
   • GDC API ( User’s Guide)

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