IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38378-9.html
   My bibliography  Save this article

Integrated genomic analysis reveals aberrations in WNT signaling in germ cell tumors of childhood and adolescence

Author

Listed:
  • Lin Xu

    (University of Texas Southwestern Medical Center
    Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Joshua L. Pierce

    (University of Texas Southwestern Medical Center)

  • Angelica Sanchez

    (University of Texas Southwestern Medical Center)

  • Kenneth S. Chen

    (University of Texas Southwestern Medical Center)

  • Abhay A. Shukla

    (University of Texas Southwestern Medical Center)

  • Nicholas J. Fustino

    (University of Texas Southwestern Medical Center
    Blank Children’s Hospital)

  • Sarai H. Stuart

    (University of Texas Southwestern Medical Center)

  • Aditya Bagrodia

    (University of Texas Southwestern Medical Center
    University of California San Diego)

  • Xue Xiao

    (University of Texas Southwestern Medical Center
    Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center)

  • Lei Guo

    (University of Texas Southwestern Medical Center
    Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center)

  • Mark D. Krailo

    (University of Southern California Keck School of Medicine
    Children’s Oncology Group)

  • Furqan Shaikh

    (The Hospital for Sick Children, University of Toronto)

  • Deborah F. Billmire

    (Riley Hospital for Children)

  • Farzana Pashankar

    (Yale University School of Medicine)

  • Jessica Bestrashniy

    (University of Minnesota)

  • J. Wolter Oosterhuis

    (Princess Máxima Center for Pediatric Oncology)

  • Ad J. M. Gillis

    (Princess Máxima Center for Pediatric Oncology)

  • Yang Xie

    (University of Texas Southwestern Medical Center
    Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Lisa Teot

    (Boston Children’s Hospital)

  • Jaume Mora

    (Sant Joan de Déu Barcelona Children’s Hospital)

  • Jenny N. Poynter

    (University of Minnesota)

  • Dinesh Rakheja

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Leendert H. J. Looijenga

    (Princess Máxima Center for Pediatric Oncology)

  • Bruce W. Draper

    (University of California Davis)

  • A. Lindsay Frazier

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

  • James F. Amatruda

    (Children’s Hospital Los Angeles
    University of Southern California Keck School of Medicine
    University of Southern California Keck School of Medicine)

Abstract

Germ cell tumors (GCTs) are neoplasms of the testis, ovary and extragonadal sites that occur in infants, children, adolescents and adults. Post-pubertal (type II) malignant GCTs may present as seminoma, non-seminoma or mixed histologies. In contrast, pre-pubertal (type I) GCTs are limited to (benign) teratoma and (malignant) yolk sac tumor (YST). Epidemiologic and molecular data have shown that pre- and post-pubertal GCTs arise by distinct mechanisms. Dedicated studies of the genomic landscape of type I and II GCT in children and adolescents are lacking. Here we present an integrated genomic analysis of extracranial GCTs across the age spectrum from 0–24 years. Activation of the WNT pathway by somatic mutation, copy-number alteration, and differential promoter methylation is a prominent feature of GCTs in children, adolescents and young adults, and is associated with poor clinical outcomes. Significantly, we find that small molecule WNT inhibitors can suppress GCT cells both in vitro and in vivo. These results highlight the importance of WNT pathway signaling in GCTs across all ages and provide a foundation for future efforts to develop targeted therapies for these cancers.

Suggested Citation

  • Lin Xu & Joshua L. Pierce & Angelica Sanchez & Kenneth S. Chen & Abhay A. Shukla & Nicholas J. Fustino & Sarai H. Stuart & Aditya Bagrodia & Xue Xiao & Lei Guo & Mark D. Krailo & Furqan Shaikh & Debor, 2023. "Integrated genomic analysis reveals aberrations in WNT signaling in germ cell tumors of childhood and adolescence," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38378-9
    DOI: 10.1038/s41467-023-38378-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38378-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38378-9?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. Amaro Taylor-Weiner & Travis Zack & Elizabeth O’Donnell & Jennifer L. Guerriero & Brandon Bernard & Anita Reddy & G. Celine Han & Saud AlDubayan & Ali Amin-Mansour & Steven E. Schumacher & Kevin Litch, 2016. "Genomic evolution and chemoresistance in germ-cell tumours," Nature, Nature, vol. 540(7631), pages 114-118, December.
    2. Linghua Wang & Shigeru Yamaguchi & Matthew D. Burstein & Keita Terashima & Kyle Chang & Ho-Keung Ng & Hideo Nakamura & Zongxiao He & Harshavardhan Doddapaneni & Lora Lewis & Mark Wang & Tomonari Suzuk, 2014. "Novel somatic and germline mutations in intracranial germ cell tumours," Nature, Nature, vol. 511(7508), pages 241-245, July.
    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. Wilfried Engl & Aliz Kunstar-Thomas & Siyi Chen & Woei Shyuan Ng & Hendrik Sielaff & Ziqing Winston Zhao, 2024. "Single-molecule imaging of SWI/SNF chromatin remodelers reveals bromodomain-mediated and cancer-mutants-specific landscape of multi-modal DNA-binding dynamics," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Thomas R. W. Oliver & Lia Chappell & Rashesh Sanghvi & Lauren Deighton & Naser Ansari-Pour & Stefan C. Dentro & Matthew D. Young & Tim H. H. Coorens & Hyunchul Jung & Tim Butler & Matthew D. C. Nevill, 2022. "Clonal diversification and histogenesis of malignant germ cell tumours," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Kyuto Sonehara & Yui Kimura & Yoshiko Nakano & Tatsuya Ozawa & Meiko Takahashi & Ken Suzuki & Takashi Fujii & Yuko Matsushita & Arata Tomiyama & Toshihiro Kishikawa & Kenichi Yamamoto & Tatsuhiko Nait, 2022. "A common deletion at BAK1 reduces enhancer activity and confers risk of intracranial germ cell tumors," Nature Communications, Nature, vol. 13(1), pages 1-9, 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_s41467-023-38378-9. 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.