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A pediatric brain tumor atlas of genes deregulated by somatic genomic rearrangement

Author

Listed:
  • Yiqun Zhang

    (Baylor College of Medicine)

  • Fengju Chen

    (Baylor College of Medicine)

  • Lawrence A. Donehower

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Michael E. Scheurer

    (Baylor College of Medicine
    Baylor College of Medicine
    Texas Children’s Hospital)

  • Chad J. Creighton

    (Baylor College of Medicine
    Baylor College of Medicine
    The University of Texas MD Anderson Cancer Center
    Baylor College of Medicine)

Abstract

The global impact of somatic structural variants (SSVs) on gene expression in pediatric brain tumors has not been thoroughly characterised. Here, using whole-genome and RNA sequencing from 854 tumors of more than 30 different types from the Children’s Brain Tumor Tissue Consortium, we report the altered expression of hundreds of genes in association with the presence of nearby SSV breakpoints. SSV-mediated expression changes involve gene fusions, altered cis-regulation, or gene disruption. SSVs considerably extend the numbers of patients with tumors somatically altered for critical pathways, including receptor tyrosine kinases (KRAS, MET, EGFR, NF1), Rb pathway (CDK4), TERT, MYC family (MYC, MYCN, MYB), and HIPPO (NF2). Compared to initial tumors, progressive or recurrent tumors involve a distinct set of SSV-gene associations. High overall SSV burden associates with TP53 mutations, histone H3.3 gene H3F3C mutations, and the transcription of DNA damage response genes. Compared to adult cancers, pediatric brain tumors would involve a different set of genes with SSV-altered cis-regulation. Our comprehensive and pan-histology genomic analyses reveal SSVs to play a major role in shaping the transcriptome of pediatric brain tumors.

Suggested Citation

  • Yiqun Zhang & Fengju Chen & Lawrence A. Donehower & Michael E. Scheurer & Chad J. Creighton, 2021. "A pediatric brain tumor atlas of genes deregulated by somatic genomic rearrangement," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21081-y
    DOI: 10.1038/s41467-021-21081-y
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    Cited by:

    1. Yiqun Zhang & Fengju Chen & Darshan S. Chandrashekar & Sooryanarayana Varambally & Chad J. Creighton, 2022. "Proteogenomic characterization of 2002 human cancers reveals pan-cancer molecular subtypes and associated pathways," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Fengju Chen & Yiqun Zhang & Darshan S. Chandrashekar & Sooryanarayana Varambally & Chad J. Creighton, 2023. "Global impact of somatic structural variation on the cancer proteome," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Fengju Chen & Yiqun Zhang & Lanlan Shen & Chad J. Creighton, 2024. "The DNA methylome of pediatric brain tumors appears shaped by structural variation and predicts survival," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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