IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43730-0.html
   My bibliography  Save this article

Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children’s Oncology Group AREN18B5-Q

Author

Listed:
  • Andrew J. Murphy

    (St. Jude Children’s Research Hospital
    University of Tennessee Health Science Center)

  • Changde Cheng

    (St. Jude Children’s Research Hospital)

  • Justin Williams

    (St. Jude Children’s Research Hospital)

  • Timothy I. Shaw

    (St. Jude Children’s Research Hospital)

  • Emilia M. Pinto

    (St. Jude Children’s Research Hospital)

  • Karissa Dieseldorff-Jones

    (St. Jude Children’s Research Hospital)

  • Jack Brzezinski

    (The Hospital for Sick Children)

  • Lindsay A. Renfro

    (Keck School of Medicine of University of Southern California)

  • Brett Tornwall

    (Children’s Oncology Group Statistics and Data Center)

  • Vicki Huff

    (The University of Texas MD Anderson Cancer Center)

  • Andrew L. Hong

    (Emory University School of Medicine)

  • Elizabeth A. Mullen

    (Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School)

  • Brian Crompton

    (Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School
    Broad Institute of Harvard and MIT)

  • Jeffrey S. Dome

    (George Washington University School of Medicine and Health Sciences)

  • Conrad V. Fernandez

    (IWK Health Center and Dalhousie University)

  • James I. Geller

    (University of Cincinnati)

  • Peter F. Ehrlich

    (University of Michigan)

  • Heather Mulder

    (St. Jude Children’s Research Hospital)

  • Ninad Oak

    (St. Jude Children’s Research Hospital)

  • Jamie Maciezsek

    (St. Jude Children’s Research Hospital)

  • Carolyn M. Jablonowski

    (St. Jude Children’s Research Hospital)

  • Andrew M. Fleming

    (St. Jude Children’s Research Hospital
    University of Tennessee Health Science Center)

  • Prahalathan Pichavaram

    (St. Jude Children’s Research Hospital)

  • Christopher L. Morton

    (St. Jude Children’s Research Hospital)

  • John Easton

    (St. Jude Children’s Research Hospital)

  • Kim E. Nichols

    (St. Jude Children’s Research Hospital)

  • Michael R. Clay

    (University of Colorado Anschutz)

  • Teresa Santiago

    (St. Jude Children’s Research Hospital)

  • Jinghui Zhang

    (St. Jude Children’s Research Hospital)

  • Jun Yang

    (St. Jude Children’s Research Hospital)

  • Gerard P. Zambetti

    (St. Jude Children’s Research Hospital)

  • Zhaoming Wang

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Andrew M. Davidoff

    (St. Jude Children’s Research Hospital
    University of Tennessee Health Science Center)

  • Xiang Chen

    (St. Jude Children’s Research Hospital)

Abstract

Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing (n = 85 tumors from 61 patients with matched germline blood DNA), RNA-seq (n = 99 tumors), and DNA methylation analysis (n = 61 peripheral blood, n = 29 non-diseased kidney, n = 99 tumors). We determine the predominant events for bilateral Wilms tumor predisposition: 1)pre-zygotic germline genetic variants readily detectable in blood DNA [WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%), and BRCA-related genes (5%)] or 2)post-zygotic epigenetic hypermethylation at 11p15.5 H19/ICR1 that may require analysis of multiple tissue types for diagnosis. Of 99 total tumor specimens, 16 (16.1%) have 11p15.5 normal retention of imprinting, 25 (25.2%) have 11p15.5 copy neutral loss of heterozygosity, and 58 (58.6%) have 11p15.5 H19/ICR1 epigenetic hypermethylation (loss of imprinting). Here, we ascertain the epigenetic and genetic modes of bilateral Wilms tumor predisposition.

Suggested Citation

  • Andrew J. Murphy & Changde Cheng & Justin Williams & Timothy I. Shaw & Emilia M. Pinto & Karissa Dieseldorff-Jones & Jack Brzezinski & Lindsay A. Renfro & Brett Tornwall & Vicki Huff & Andrew L. Hong , 2023. "Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children’s Oncology Group AREN18B5-Q," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43730-0
    DOI: 10.1038/s41467-023-43730-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43730-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43730-0?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
    ---><---

    References listed on IDEAS

    as
    1. Andrew J. Murphy & Xiang Chen & Emilia M. Pinto & Justin S. Williams & Michael R. Clay & Stanley B. Pounds & Xueyuan Cao & Lei Shi & Tong Lin & Geoffrey Neale & Christopher L. Morton & Mary A. Woolard, 2019. "Forty-five patient-derived xenografts capture the clinical and biological heterogeneity of Wilms tumor," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    2. Ankur Chakravarthy & Andrew Furness & Kroopa Joshi & Ehsan Ghorani & Kirsty Ford & Matthew J. Ward & Emma V. King & Matt Lechner & Teresa Marafioti & Sergio A. Quezada & Gareth J. Thomas & Andrew Febe, 2018. "Pan-cancer deconvolution of tumour composition using DNA methylation," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    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.
    1. Marjan M. Naeini & Felicity Newell & Lauren G. Aoude & Vanessa F. Bonazzi & Kalpana Patel & Guy Lampe & Lambros T. Koufariotis & Vanessa Lakis & Venkateswar Addala & Olga Kondrashova & Rebecca L. John, 2023. "Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Ankur Chakravarthy & Ian Reddin & Stephen Henderson & Cindy Dong & Nerissa Kirkwood & Maxmilan Jeyakumar & Daniela Rothschild Rodriguez & Natalia Gonzalez Martinez & Jacqueline McDermott & Xiaoping Su, 2022. "Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Caroline Hoffmann & Floriane Noel & Maximilien Grandclaudon & Lucile Massenet-Regad & Paula Michea & Philemon Sirven & Lilith Faucheux & Aurore Surun & Olivier Lantz & Mylene Bohec & Jian Ye & Weihua , 2022. "PD-L1 and ICOSL discriminate human Secretory and Helper dendritic cells in cancer, allergy and autoimmunity," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    4. Grayson A. Herrgott & James M. Snyder & Ruicong She & Tathiane M. Malta & Thais S. Sabedot & Ian Y. Lee & Jacob Pawloski & Guilherme G. Podolsky-Gondim & Karam P. Asmaro & Jiaqi Zhang & Cara E. Cannel, 2023. "Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    5. Funan He & Abhik M. Bandyopadhyay & Laura J. Klesse & Anna Rogojina & Sang H. Chun & Erin Butler & Taylor Hartshorne & Trevor Holland & Dawn Garcia & Korri Weldon & Luz-Nereida Perez Prado & Anne-Mari, 2023. "Genomic profiling of subcutaneous patient-derived xenografts reveals immune constraints on tumor evolution in childhood solid cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, 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:14:y:2023:i:1:d:10.1038_s41467-023-43730-0. 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.

    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.