The genomic landscape of pediatric acute lymphoblastic leukemia

Nature Genetics. Volume 54, Issue 9 ;p:1376-1389, 1 September 2022, 10.1038/s41588-022-01159-z

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Here, using whole-genome, exome and transcriptome sequencing of 2,754 childhood patients with ALL, we find that, despite a generally low mutation burden, ALL cases harbor a median of four putative somatic driver alterations per sample, with 376 putative driver genes identified varying in prevalence across ALL subtypes. Most samples harbor at least one rare gene alteration, including 70 putative cancer driver genes associated with ubiquitination, SUMOylation, noncoding transcripts and other functions. In hyperdiploid B-ALL, chromosomal gains are acquired early and synchronously before ultraviolet-induced mutation. By contrast, ultraviolet-induced mutations precede chromosomal gains in B-ALL cases with intrachromosomal amplification of chromosome 21. We also demonstrate the prognostic significance of genetic alterations within subtypes. Intriguingly, DUX4- and KMT2A-rearranged subtypes separate into CEBPA/FLT3- or NFATC4-expressing subgroups with potential clinical implications. Together, these results deepen understanding of the ALL genomic landscape and associated outcomes.

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Supplemental Data Files

• GDC Manifests
  • Controlled-Access Data Download Manifest (6 Files)
  • Open-Access Data Download Manifest (22 Files)
  • WGS CGI Files Download Manifest (305 Files)
• Copy Number
  • TARGET ALL P2 Copy Number Array Level 1 Data (Controlled)
  • TARGET ALL P2 Copy Number Array Level 2 Data (Controlled)
  • TARGET ALL P2 Copy Number Array Level 3 Data
  • TARGET ALL P2 Copy Number Array Metadata
• Gene Expression Array
  • TARGET ALL P2 Gene Expression Array Level 1 Data
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  • TARGET ALL P2 Gene Expression Array Level 3 Data
  • TARGET ALL P2 Gene Expression Array Metadata
• Methylation Array
  • TARGET ALL P2 Methylation Array Level 1 Data
  • TARGET ALL P2 Methylation Array Level 1 Data (Controlled)
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  • TARGET ALL P2 Methylation Array Level 3 Data
  • TARGET ALL P2 Methylation Array Design Information
  • TARGET ALL P2 Methylation Array Metadata
• mRNA-Seq
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  • TARGET ALL P2 mRNA-Seq Level 3 Data (Controlled)
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• miRNA-Seq
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• WGS
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  • TARGET ALL P1 and P2 WGS L3 Data (Controlled)
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  • TARGET ALL P2 and P2 WGS Metadata
• WXS
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  • TARGET ALL P2 WXS Level 3 Data (Controlled)
  • TARGET ALL P2 WXS Design Information
  • TARGET ALL P2 WXS Metadata
• Miscellaneous Files
  • TARGET ALL P2 Sample Matrix

Additional Resources

• TARGET-ALL-P2 at SRA (link is external) NCBI

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