Pan-cancer genome and transcriptome analyses of 1699 paediatric leukaemias and solid tumours

Nature. Volume 555(7696): p.371-376, 15 March 2018, 10.1038/nature25795

Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes that are dysregulated in cancer cells from diverse lineages. Pan-cancer analyses have been performed for adult but not paediatric cancers, which commonly occur in developing mesodermic rather than adult epithelial tissues. Here we present a pan-cancer study of somatic alterations, including single nucleotide variants, small insertions or deletions, structural variations, copy number alterations, gene fusions and internal tandem duplications in 1,699 paediatric leukaemias and solid tumours across six histotypes, with whole-genome, whole-exome and transcriptome sequencing data processed under a uniform analytical framework. We report 142 driver genes in paediatric cancers, of which only 45% match those found in adult pan-cancer studies; copy number alterations and structural variants constituted the majority (62%) of events. Eleven genome-wide mutational signatures were identified, including one attributed to ultraviolet-light exposure in eight aneuploid leukaemias. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% exhibited allele-specific expression. These data provide a comprehensive genomic architecture for paediatric cancers and emphasize the need for paediatric cancer-specific development of precision therapies.

Supplemental Data

• GDC Manifests
  • Controlled-Access Data Download Manifest (18 Files)
  • Open-Access Data Download Manifest (42 Files)
  • ReadMe Files Download Manifest (32 Files)

• Copy Number Array
  • TARGET OS Copy number array Level 1 Data (Controlled)
  • TARGET OS Copy number array Level 2 Data (Controlled)
  • TARGET OS Copy number array Level 3 Data
  • TARGET OS Copy number array Level 4 Data
  • TARGET OS Copy number array Metadata
  • TARGET OS Copy Number Array Level 1 (Controlled) - Toronto Cases
  • TARGET OS Copy Number Array Level 2 (Controlled) - Toronto Cases
  • TARGET OS Copy Number Array Level 3 - Toronto Cases
  • TARGET OS Copy Number Array Metadata - Toronto Cases
• Gene Expression Array
  • TARGET OS Gene expression array Level 1 Data (Controlled)
  • TARGET OS Gene expression array Level 2 Data (Controlled)
  • TARGET OS Gene expression array Level 3 Data
  • TARGET OS Gene expression array Metadata
  • TARGET OS Gene Expression Array Metadata - Brazil Cases
  • TARGET OS Gene Expression Array Level 1 (Controlled) - Toronto Cases
  • TARGET OS Gene Expression Array Metadata - Toronto Cases
• mRNA-Seq
  • TARGET OS mRNA-Seq Level 3 data
  • TARGET OS mRNA-Seq Level 4 data
  • TARGET OS mRNA-Seq Level 3 data (Controlled)
  • TARGET OS mRNA-Seq Metadata
  • TARGET OS mRNA-Seq Level 1 (Controlled) - Toronto Cases
  • TARGET OS mRNA-Seq Level 3 - Toronto Cases
  • TARGET OS mRNA-Seq Metadata - Toronto Cases
• miRNA-Seq
  • TARGET OS miRNA-Seq Level 1 Data
  • TARGET OS miRNA-Seq Level 2 Data
  • TARGET OS miRNA-Seq Metadata
  • TARGET OS miRNA-PCR Level 1 - Brazil Cases
  • TARGET OS miRNA-PCR Level 2 - Brazil Cases
  • TARGET OS miRNA-PCR Metadata - Brazil Cases
  • TARGET OS miRNA-PCR Level 1 - Toronto Cases
  • TARGET OS miRNA-PCR Level 2 - Toronto Cases
  • TARGET OS miRNA-PCR Metadata - Toronto Cases
• Whole Exome Sequencing
  • TARGET OS WXS Level 4 Data
  • TARGET OS WXS Level 3 Data (Controlled)
  • TARGET OS WXS Design
  • TARGET OS WXS Metadata
  • TARGET OS WXS Level 3 (Controlled)
  • TARGET OS WXS Metadata - Toronto Cases
• Methylation Array
  • TARGET OS Methylation array Level 1 Data (Controlled)
  • TARGET OS Methylation array Level 2 Data
  • TARGET OS Methylation array Level 3 Data
  • TARGET OS Methylation array Metadata
  • TARGET OS Methylation Array Level 1 (Controlled) - Brazil Cases
  • TARGET OS Methylation Array Level 2 - Brazil Cases
  • TARGET OS Methylation Array Level 3 - Brazil Cases
  • TARGET OS Methylation Array Metadata - Brazil Cases
  • TARGET OS Methylation Array Level 1 (Controlled) - Toronto Cases
  • TARGET OS Methylation Array Level 2 - Toronto Cases
  • TARGET OS Methylation Array Level 3 - Toronto Cases
  • TARGET OS Methylation Array Metadata - Toronto Cases
• Whole Genome Sequencing
  • TARGET OS WGS Level 3 Data
  • TARGET OS WGS Level 3 Data (Controlled)
  • TARGET OS WGS Level 4 Data
  • TARGET OS WGS Metadata
  • TARGET OS WGS Level 3 (Controlled) - Toronto Cases
• Targeted Capture Sequencing
  • TARGET OS Targeted Capture Sequencing Level 3 Data (Controlled)
  • TARGET OS Targeted Capture Sequencing Design
  • TARGET OS Targeted Capture Sequencing Metadata
• Miscellaneous Files
  • TARGET OS Sample Matrices
  • TARGET OS CGI README (Controlled)
  • TARGET OS CGI Requested Reports (Controlled)

Additional Resources

• OCG TARGET Data Matrix (link is external) Office of Cancer Genomics
• TARGET-WT 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)
3. Use the manifest file and token to download data using the GDC DTT or the GDC API
   • GDC DTT ( Download, User’s Guide)
   • GDC API ( User’s Guide)

For assistance, please contact the GDC Help Desk: support@nci-gdc.datacommons.io.