IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-07041-z.html
   My bibliography  Save this article

Whole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer

Author

Listed:
  • Naveed Ishaque

    (DKFZ-HIPO, DKFZ, Im Neuenheimer Feld 580
    German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT)
    German Cancer Research Center (DKFZ))

  • Mohammed L. Abba

    (Medical Faculty Mannheim, Ruprecht Karls University Heidelberg
    Centre for Biomedicine and Medical Technology Mannheim (CBTM))

  • Christine Hauser

    (Medical Faculty Mannheim, Ruprecht Karls University Heidelberg
    Centre for Biomedicine and Medical Technology Mannheim (CBTM))

  • Nitin Patil

    (Medical Faculty Mannheim, Ruprecht Karls University Heidelberg
    Centre for Biomedicine and Medical Technology Mannheim (CBTM))

  • Nagarajan Paramasivam

    (German Cancer Research Center (DKFZ)
    Ruprecht Karls University Heidelberg)

  • Daniel Huebschmann

    (German Cancer Research Center (DKFZ))

  • Jörg Hendrik Leupold

    (Medical Faculty Mannheim, Ruprecht Karls University Heidelberg
    Centre for Biomedicine and Medical Technology Mannheim (CBTM))

  • Gnana Prakash Balasubramanian

    (German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT))

  • Kortine Kleinheinz

    (German Cancer Research Center (DKFZ))

  • Umut H. Toprak

    (German Cancer Research Center (DKFZ))

  • Barbara Hutter

    (German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT))

  • Axel Benner

    (German Cancer Research Centre (DKFZ))

  • Anna Shavinskaya

    (Medical Faculty Mannheim, Ruprecht Karls University Heidelberg)

  • Chan Zhou

    (Medical Faculty Mannheim, Ruprecht Karls University Heidelberg
    Centre for Biomedicine and Medical Technology Mannheim (CBTM))

  • Zuguang Gu

    (DKFZ-HIPO, DKFZ, Im Neuenheimer Feld 580
    German Cancer Research Center (DKFZ))

  • Jules Kerssemakers

    (German Cancer Research Center (DKFZ))

  • Alexander Marx

    (University Hospital Mannheim (UMM))

  • Marcin Moniuszko

    (Medical University of Bialystok)

  • Miroslaw Kozlowski

    (Medical University of Bialystok)

  • Joanna Reszec

    (Medical University of Bialystok)

  • Jacek Niklinski

    (Medical University of Bialystok)

  • Jürgen Eils

    (German Cancer Research Center (DKFZ))

  • Matthias Schlesner

    (German Cancer Research Center (DKFZ)
    German Cancer Research Center (DKFZ))

  • Roland Eils

    (DKFZ-HIPO, DKFZ, Im Neuenheimer Feld 580
    German Cancer Research Center (DKFZ)
    Ruprecht Karls University Heidelberg)

  • Benedikt Brors

    (German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT)
    German Cancer Consortium (DKTK))

  • Heike Allgayer

    (Medical Faculty Mannheim, Ruprecht Karls University Heidelberg
    Centre for Biomedicine and Medical Technology Mannheim (CBTM))

Abstract

Incomplete understanding of the metastatic process hinders personalized therapy. Here we report the most comprehensive whole-genome study of colorectal metastases vs. matched primary tumors. 65% of somatic mutations originate from a common progenitor, with 15% being tumor- and 19% metastasis-specific, implicating a higher mutation rate in metastases. Tumor- and metastasis-specific mutations harbor elevated levels of BRCAness. We confirm multistage progression with new components ARHGEF7/ARHGEF33. Recurrently mutated non-coding elements include ncRNAs RP11-594N15.3, AC010091, SNHG14, 3’ UTRs of FOXP2, DACH2, TRPM3, XKR4, ANO5, CBL, CBLB, the latter four potentially dual protagonists in metastasis and efferocytosis-/PD-L1 mediated immunosuppression. Actionable metastasis-specific lesions include FAT1, FGF1, BRCA2, KDR, and AKT2-, AKT3-, and PDGFRA-3’ UTRs. Metastasis specific mutations are enriched in PI3K-Akt signaling, cell adhesion, ECM and hepatic stellate activation genes, suggesting genetic programs for site-specific colonization. Our results put forward hypotheses on tumor and metastasis evolution, and evidence for metastasis-specific events relevant for personalized therapy.

Suggested Citation

  • Naveed Ishaque & Mohammed L. Abba & Christine Hauser & Nitin Patil & Nagarajan Paramasivam & Daniel Huebschmann & Jörg Hendrik Leupold & Gnana Prakash Balasubramanian & Kortine Kleinheinz & Umut H. To, 2018. "Whole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07041-z
    DOI: 10.1038/s41467-018-07041-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-07041-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-07041-z?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. Zhe Jiang & YoungJun Ju & Amjad Ali & Philip E. D. Chung & Patryk Skowron & Dong-Yu Wang & Mariusz Shrestha & Huiqin Li & Jeff C. Liu & Ioulia Vorobieva & Ronak Ghanbari-Azarnier & Ethel Mwewa & Maria, 2023. "Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. 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:9:y:2018:i:1:d:10.1038_s41467-018-07041-z. 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.