IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-019-13885-w.html
   My bibliography  Save this article

High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations

Author

Listed:
  • Yiqun Zhang

    (Baylor College of Medicine)

  • Fengju Chen

    (Baylor College of Medicine)

  • Nuno A. Fonseca

    (European Bioinformatics Institute, (EMBL-EBI)
    Universidade do Porto)

  • Yao He

    (Peking University
    Peking University)

  • Masashi Fujita

    (RIKEN Center for Integrative Medical Sciences)

  • Hidewaki Nakagawa

    (RIKEN Center for Integrative Medical Sciences)

  • Zemin Zhang

    (Peking University
    Peking University)

  • Alvis Brazma

    (European Bioinformatics Institute, (EMBL-EBI))

  • Chad J. Creighton

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

Abstract

The impact of somatic structural variants (SVs) on gene expression in cancer is largely unknown. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data and RNA sequencing from a common set of 1220 cancer cases, we report hundreds of genes for which the presence within 100 kb of an SV breakpoint associates with altered expression. For the majority of these genes, expression increases rather than decreases with corresponding breakpoint events. Up-regulated cancer-associated genes impacted by this phenomenon include TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. TERT-associated breakpoints involve ~3% of cases, most frequently in liver biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involve ~1% of non-amplified cases. For many genes, SVs are significantly associated with increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the promoter is often increased with nearby SV breakpoint, which may involve inactivation of repressor elements.

Suggested Citation

  • Yiqun Zhang & Fengju Chen & Nuno A. Fonseca & Yao He & Masashi Fujita & Hidewaki Nakagawa & Zemin Zhang & Alvis Brazma & Chad J. Creighton, 2020. "High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13885-w
    DOI: 10.1038/s41467-019-13885-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-13885-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-13885-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. 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.
    2. 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.
    3. Josefine Radke & Naveed Ishaque & Randi Koll & Zuguang Gu & Elisa Schumann & Lina Sieverling & Sebastian Uhrig & Daniel Hübschmann & Umut H. Toprak & Cristina López & Xavier Pastor Hostench & Simone B, 2022. "The genomic and transcriptional landscape of primary central nervous system lymphoma," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13885-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.