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Epigenetic Alterations of Repeated Relapses in Patient-matched Childhood Ependymomas

Author

Listed:
  • Sibo Zhao

    (Texas Children’s Hospital, Baylor College of Medicine
    Texas Children’s Hospital, Baylor College of Medicine
    Cook Children’s Medical Center
    Cook Children’s Medical Center)

  • Jia Li

    (Texas A&M University
    Texas A&M University
    Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University; and Guangzhou Laboratory, Bioland)

  • Huiyuan Zhang

    (Texas Children’s Hospital, Baylor College of Medicine
    Texas Children’s Hospital, Baylor College of Medicine)

  • Lin Qi

    (Texas Children’s Hospital, Baylor College of Medicine
    Texas Children’s Hospital, Baylor College of Medicine
    Northwestern University Feinberg School of Medicine)

  • Yuchen Du

    (Texas Children’s Hospital, Baylor College of Medicine
    Texas Children’s Hospital, Baylor College of Medicine
    Northwestern University Feinberg School of Medicine)

  • Mari Kogiso

    (Texas Children’s Hospital, Baylor College of Medicine
    Texas Children’s Hospital, Baylor College of Medicine)

  • Frank K. Braun

    (Texas Children’s Hospital, Baylor College of Medicine
    Texas Children’s Hospital, Baylor College of Medicine)

  • Sophie Xiao

    (Northwestern University Feinberg School of Medicine)

  • Yulun Huang

    (Texas Children’s Hospital, Baylor College of Medicine
    Texas Children’s Hospital, Baylor College of Medicine
    the First Affiliated Hospital, and Department of Neurosurgery, Dushu Lake Hospital, Suzhou Medical College, Soochow University)

  • Jianfang Li

    (Texas A&M University)

  • Wan-Yee Teo

    (National Cancer Center Singapore
    Duke-NUS Medical School Singapore
    KK Women’s & Children’s Hospital Singapore
    Institute of Molecular and Cell Biology, A*STAR)

  • Holly Lindsay

    (Texas Children’s Hospital, Baylor College of Medicine
    Texas Children’s Hospital, Baylor College of Medicine)

  • Patricia Baxter

    (Texas Children’s Hospital, Baylor College of Medicine)

  • Jack M. F. Su

    (Texas Children’s Hospital, Baylor College of Medicine)

  • Adekunle Adesina

    (Baylor College of Medicine)

  • Miklós Laczik

    (Epigenetic Services)

  • Paola Genevini

    (Epigenetic Services)

  • Anne-Clemence Veillard

    (Epigenetic Services)

  • Sol Schvartzman

    (Epigenetic Services)

  • Geoffrey Berguet

    (Epigenetic Services)

  • Shi-Rong Ding

    (Sun Yat-sen University Cancer Center)

  • Liping Du

    (Northwestern University Feinberg School of Medicine)

  • Clifford Stephan

    (Texas A&M University)

  • Jianhua Yang

    (Texas Children’s Hospital, Baylor College of Medicine)

  • Peter J. A. Davies

    (Texas A&M University)

  • Xinyan Lu

    (Northwestern University Feinberg School of Medicine)

  • Murali Chintagumpala

    (Texas Children’s Hospital, Baylor College of Medicine)

  • Donald William Parsons

    (Texas Children’s Hospital, Baylor College of Medicine)

  • Laszlo Perlaky

    (Texas Children’s Hospital, Baylor College of Medicine)

  • Yun-Fei Xia

    (Sun Yat-sen University Cancer Center)

  • Tsz-Kwong Man

    (Texas Children’s Hospital, Baylor College of Medicine)

  • Yun Huang

    (Texas A&M University)

  • Deqiang Sun

    (Texas A&M University)

  • Xiao-Nan Li

    (Texas Children’s Hospital, Baylor College of Medicine
    Texas Children’s Hospital, Baylor College of Medicine
    Northwestern University Feinberg School of Medicine)

Abstract

Recurrence is frequent in pediatric ependymoma (EPN). Our longitudinal integrated analysis of 30 patient-matched repeated relapses (3.67 ± 1.76 times) over 13 years (5.8 ± 3.8) reveals stable molecular subtypes (RELA and PFA) and convergent DNA methylation reprogramming during serial relapses accompanied by increased orthotopic patient derived xenograft (PDX) (13/27) formation in the late recurrences. A set of differentially methylated CpGs (DMCs) and DNA methylation regions (DMRs) are found to persist in primary and relapse tumors (potential driver DMCs) and are acquired exclusively in the relapses (potential booster DMCs). Integrating with RNAseq reveals differentially expressed genes regulated by potential driver DMRs (CACNA1H, SLC12A7, RARA in RELA and HSPB8, GMPR, ITGB4 in PFA) and potential booster DMRs (PLEKHG1 in RELA and NOTCH, EPHA2, SUFU, FOXJ1 in PFA tumors). DMCs predicators of relapse are also identified in the primary tumors. This study provides a high-resolution epigenetic roadmap of serial EPN relapses and 13 orthotopic PDX models to facilitate biological and preclinical studies.

Suggested Citation

  • Sibo Zhao & Jia Li & Huiyuan Zhang & Lin Qi & Yuchen Du & Mari Kogiso & Frank K. Braun & Sophie Xiao & Yulun Huang & Jianfang Li & Wan-Yee Teo & Holly Lindsay & Patricia Baxter & Jack M. F. Su & Adeku, 2022. "Epigenetic Alterations of Repeated Relapses in Patient-matched Childhood Ependymomas," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34514-z
    DOI: 10.1038/s41467-022-34514-z
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