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Genetic changes associated with relapse in favorable histology Wilms tumor: A Children's Oncology Group AREN03B2 study

  1. Author:
    Gadd, Samantha
    Huff, Vicki
    Skol, Andrew D
    Renfro, Lindsay A
    Fernandez, Conrad V
    Mullen, Elizabeth A
    Jones, Corbin D
    Hoadley, Katherine A
    Yap, Kai Lee
    Ramirez, Nilsa C
    Aris, Sheena
    Phung, Quy H
    Perlman, Elizabeth J

  2. Author Address

    Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children 39;s Hospital of Chicago and Robert H. Lurie Cancer Center, Northwestern University, 225 East Chicago Avenue, Box 17, Chicago, IL 60611, USA., Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Division of Biostatistics, University of Southern California, Los Angeles, CA 90007, USA., Department of Pediatrics, IWK Health Centre and Dalhousie University, Halifax, NS B3K 6R8, Canada., Department of Pediatric Oncology, Dana-Farber/Boston Children 39;s Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA 02215, USA., Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Institute for Genomic Medicine and Biopathology Center, Nationwide Children 39;s Hospital, Departments of Pathology and Pediatrics, Ohio State University, Columbus, OH 43205, USA., Biospecimen Research Group, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children 39;s Hospital of Chicago and Robert H. Lurie Cancer Center, Northwestern University, 225 East Chicago Avenue, Box 17, Chicago, IL 60611, USA. Electronic address: eperlman@luriechildrens.org.,
    1. Year: 2022
    2. Date: May 25
    3. Epub Date: 2022 05 25
  2. Journal: Cell Reports. Medicine
    1. Pages: 100644
  4. Type of Article: Article
  5. Article Number: 100644
  1. Abstract:

    Over the last decade, sequencing of primary tumors has clarified the genetic underpinnings of Wilms tumor but has not affected therapy, outcome, or toxicity. We now sharpen our focus on relapse samples from the umbrella AREN03B2 study. We show that over 40% of relapse samples contain mutations in SIX1 or genes of the MYCN network, drivers of progenitor proliferation. Not previously seen in large studies of primary Wilms tumors, DIS3 and TERT are now identified as recurrently mutated. The analysis of primary-relapse tumor pairs suggests that 11p15 loss of heterozygosity (and other copy number changes) and mutations in WT1 and MLLT1 typically occur early, but mutations in SIX1, MYCN, and WTX are late developments in some individuals. Most strikingly, 75% of relapse samples had gain of 1q, providing strong conceptual support for studying circulating tumor DNA in clinical trials to better detect 1q gain earlier and monitor response. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

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External Sources

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  2. DOI: 10.1016/j.xcrm.2022.100644
  3. PMID: 35617957
  4. PII : S2666-3791(22)00169-0

Library Notes

  1. Fiscal Year: FY2021-2022
  2. Group/Lab/Department: Biospecimen Research Group
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