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Genomic profiling of subcutaneous patient-derived xenografts reveals immune constraints on tumor evolution in childhood solid cancer

Author

Listed:
  • Funan He

    (University of Texas Health Science Center
    University of Texas Health Science Center)

  • Abhik M. Bandyopadhyay

    (University of Texas Health Science Center)

  • Laura J. Klesse

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    Children’s Health Children’s Medical Center)

  • Anna Rogojina

    (University of Texas Health Science Center)

  • Sang H. Chun

    (University of Texas Health Science Center)

  • Erin Butler

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    Children’s Health Children’s Medical Center)

  • Taylor Hartshorne

    (University of Texas Southwestern Medical Center)

  • Trevor Holland

    (University of Texas Health Science Center)

  • Dawn Garcia

    (University of Texas Health Science Center)

  • Korri Weldon

    (University of Texas Health Science Center)

  • Luz-Nereida Perez Prado

    (University of Texas Health Science Center)

  • Anne-Marie Langevin

    (University of Texas Health Science Center
    University of Texas Health Science Center)

  • Allison C. Grimes

    (University of Texas Health Science Center
    University of Texas Health Science Center)

  • Aaron Sugalski

    (University of Texas Health Science Center)

  • Shafqat Shah

    (University of Texas Health Science Center)

  • Chatchawin Assanasen

    (University of Texas Health Science Center
    University of Texas Health Science Center)

  • Zhao Lai

    (University of Texas Health Science Center
    University of Texas Health Science Center
    University of Texas Health Science Center)

  • Yi Zou

    (University of Texas Health Science Center)

  • Dias Kurmashev

    (University of Texas Health Science Center)

  • Lin Xu

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

  • Yang Xie

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

  • Yidong Chen

    (University of Texas Health Science Center
    University of Texas Health Science Center
    University of Texas Health Science Center)

  • Xiaojing Wang

    (University of Texas Health Science Center
    University of Texas Health Science Center
    University of Texas Health Science Center)

  • Gail E. Tomlinson

    (University of Texas Health Science Center
    University of Texas Health Science Center
    University of Texas Health Science Center)

  • Stephen X. Skapek

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    Children’s Health Children’s Medical Center)

  • Peter J. Houghton

    (University of Texas Health Science Center
    University of Texas Health Science Center
    University of Texas Health Science Center)

  • Raushan T. Kurmasheva

    (University of Texas Health Science Center
    University of Texas Health Science Center
    University of Texas Health Science Center)

  • Siyuan Zheng

    (University of Texas Health Science Center
    University of Texas Health Science Center
    University of Texas Health Science Center)

Abstract

Subcutaneous patient-derived xenografts (PDXs) are an important tool for childhood cancer research. Here, we describe a resource of 68 early passage PDXs established from 65 pediatric solid tumor patients. Through genomic profiling of paired PDXs and patient tumors (PTs), we observe low mutational similarity in about 30% of the PT/PDX pairs. Clonal analysis in these pairs show an aggressive PT minor subclone seeds the major clone in the PDX. We show evidence that this subclone is more immunogenic and is likely suppressed by immune responses in the PT. These results suggest interplay between intratumoral heterogeneity and antitumor immunity may underlie the genetic disparity between PTs and PDXs. We further show that PDXs generally recapitulate PTs in copy number and transcriptomic profiles. Finally, we report a gene fusion LRPAP1-PDGFRA. In summary, we report a childhood cancer PDX resource and our study highlights the role of immune constraints on tumor evolution.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43373-1
    DOI: 10.1038/s41467-023-43373-1
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    References listed on IDEAS

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