IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-06206-0.html
   My bibliography  Save this article

Analysis of extracellular mRNA in human urine reveals splice variant biomarkers of muscular dystrophies

Author

Listed:
  • Layal Antoury

    (Massachusetts General Hospital
    Harvard Medical School)

  • Ningyan Hu

    (Massachusetts General Hospital
    Harvard Medical School)

  • Leonora Balaj

    (Massachusetts General Hospital
    Harvard Medical School)

  • Sudeshna Das

    (Massachusetts General Hospital
    Harvard Medical School)

  • Sofia Georghiou

    (Harvard Medical School
    Boston Children’s Hospital)

  • Basil Darras

    (Harvard Medical School
    Boston Children’s Hospital)

  • Tim Clark

    (Massachusetts General Hospital
    Harvard Medical School)

  • Xandra O. Breakefield

    (Massachusetts General Hospital
    Harvard Medical School
    Massachusetts General Hospital)

  • Thurman M. Wheeler

    (Massachusetts General Hospital
    Harvard Medical School)

Abstract

Urine contains extracellular RNA (exRNA) markers of urogenital cancers. However, the capacity of genetic material in urine to identify systemic diseases is unknown. Here we describe exRNA splice products in human urine as a source of biomarkers for the two most common forms of muscular dystrophies, myotonic dystrophy (DM) and Duchenne muscular dystrophy (DMD). Using a training set, RT-PCR, droplet digital PCR, and principal component regression, we identify ten transcripts that are spliced differently in urine exRNA from patients with DM type 1 (DM1) as compared to unaffected or disease controls, form a composite biomarker, and develop a predictive model that is 100% accurate in our independent validation set. Urine also contains mutation-specific DMD mRNAs that confirm exon-skipping activity of the antisense oligonucleotide drug eteplirsen. Our results establish that urine mRNA splice variants can be used to monitor systemic diseases with minimal or no clinical effect on the urinary tract.

Suggested Citation

  • Layal Antoury & Ningyan Hu & Leonora Balaj & Sudeshna Das & Sofia Georghiou & Basil Darras & Tim Clark & Xandra O. Breakefield & Thurman M. Wheeler, 2018. "Analysis of extracellular mRNA in human urine reveals splice variant biomarkers of muscular dystrophies," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06206-0
    DOI: 10.1038/s41467-018-06206-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-06206-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-06206-0?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. Ningyan Hu & Eunjoo Kim & Layal Antoury & Thurman M. Wheeler, 2023. "Correction of Clcn1 alternative splicing reverses muscle fiber type transition in mice with myotonic dystrophy," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Mathula Thangarajh & Aiping Zhang & Kirandeep Gill & Habtom W Ressom & Zhenzhi Li & Rency S Varghese & Eric P Hoffman & Kanneboyina Nagaraju & Yetrib Hathout & Simina M Boca, 2019. "Discovery of potential urine-accessible metabolite biomarkers associated with muscle disease and corticosteroid response in the mdx mouse model for Duchenne," PLOS ONE, Public Library of Science, vol. 14(7), pages 1-17, July.

    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_s41467-018-06206-0. 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.