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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
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    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)

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