IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-57271-1.html
   My bibliography  Save this article

Pan-cancer multi-omic model of LINE-1 activity reveals locus heterogeneity of retrotransposition efficiency

Author

Listed:
  • Alexander Solovyov

    (Memorial Sloan Kettering Cancer Center)

  • Julie M. Behr

    (Inc.)

  • David Hoyos

    (Memorial Sloan Kettering Cancer Center)

  • Eric Banks

    (Inc.
    Acorn Biosciences)

  • Alexander W. Drong

    (Inc.)

  • Bryan Thornlow

    (Inc.)

  • Jimmy Z. Zhong

    (Inc.)

  • Enrique Garcia-Rivera

    (Inc.)

  • Wilson McKerrow

    (Inc.)

  • Chong Chu

    (Inc.)

  • Cedric Arisdakessian

    (Inc.)

  • Dennis M. Zaller

    (Inc.)

  • Junne Kamihara

    (Boston Children’s Hospital
    Harvard Medical School
    Harvard Medical School)

  • Liyang Diao

    (Inc.)

  • Menachem Fromer

    (Inc.)

  • Benjamin D. Greenbaum

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

Abstract

Somatic mobilization of LINE-1 (L1) has been implicated in cancer etiology. We analyzed a recent TCGA data release comprised of nearly 5000 pan-cancer paired tumor-normal whole-genome sequencing (WGS) samples and ~9000 tumor RNA samples. We developed TotalReCall an improved algorithm and pipeline for detection of L1 retrotransposition (RT), finding high correlation between L1 expression and “RT burden” per sample. Furthermore, we mathematically model the dual regulatory roles of p53, where mutations in TP53 disrupt regulation of both L1 expression and retrotransposition. We found those with Li-Fraumeni Syndrome (LFS) heritable TP53 pathogenic and likely pathogenic variants bear similarly high L1 activity compared to matched cancers from patients without LFS, suggesting this population be considered in attempts to target L1 therapeutically. Due to improved sensitivity, we detect over 10 genes beyond TP53 whose mutations correlate with L1, including ATRX, suggesting other, potentially targetable, mechanisms underlying L1 regulation in cancer remain to be discovered.

Suggested Citation

  • Alexander Solovyov & Julie M. Behr & David Hoyos & Eric Banks & Alexander W. Drong & Bryan Thornlow & Jimmy Z. Zhong & Enrique Garcia-Rivera & Wilson McKerrow & Chong Chu & Cedric Arisdakessian & Denn, 2025. "Pan-cancer multi-omic model of LINE-1 activity reveals locus heterogeneity of retrotransposition efficiency," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57271-1
    DOI: 10.1038/s41467-025-57271-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-57271-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-57271-1?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
    ---><---

    References listed on IDEAS

    as
    1. Eric T. Baldwin & Trevor van Eeuwen & David Hoyos & Arthur Zalevsky & Egor P. Tchesnokov & Roberto Sánchez & Bryant D. Miller & Luciano H. Di Stefano & Francesc Xavier Ruiz & Matthew Hancock & Esin Iş, 2024. "Structures, functions and adaptations of the human LINE-1 ORF2 protein," Nature, Nature, vol. 626(7997), pages 194-206, February.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.

      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:16:y:2025:i:1:d:10.1038_s41467-025-57271-1. 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.

      If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.