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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

    as
    1. Genta Nagae & Shogo Yamamoto & Masashi Fujita & Takanori Fujita & Aya Nonaka & Takayoshi Umeda & Shiro Fukuda & Kenji Tatsuno & Kazuhiro Maejima & Akimasa Hayashi & Sho Kurihara & Masato Kojima & Tomo, 2021. "Genetic and epigenetic basis of hepatoblastoma diversity," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    2. Kosuke Yoshihara & Maria Shahmoradgoli & Emmanuel Martínez & Rahulsimham Vegesna & Hoon Kim & Wandaliz Torres-Garcia & Victor Treviño & Hui Shen & Peter W. Laird & Douglas A. Levine & Scott L. Carter , 2013. "Inferring tumour purity and stromal and immune cell admixture from expression data," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
    3. Hua Sun & Song Cao & R. Jay Mashl & Chia-Kuei Mo & Simone Zaccaria & Michael C. Wendl & Sherri R. Davies & Matthew H. Bailey & Tina M. Primeau & Jeremy Hoog & Jacqueline L. Mudd & Dennis A. Dean & Raj, 2021. "Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    4. Elizabeth Stewart & Sara M. Federico & Xiang Chen & Anang A. Shelat & Cori Bradley & Brittney Gordon & Asa Karlstrom & Nathaniel R. Twarog & Michael R. Clay & Armita Bahrami & Burgess B. Freeman & Bei, 2017. "Orthotopic patient-derived xenografts of paediatric solid tumours," Nature, Nature, vol. 549(7670), pages 96-100, September.
    5. 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.
    6. Michael S. Lawrence & Petar Stojanov & Paz Polak & Gregory V. Kryukov & Kristian Cibulskis & Andrey Sivachenko & Scott L. Carter & Chip Stewart & Craig H. Mermel & Steven A. Roberts & Adam Kiezun & Pe, 2013. "Mutational heterogeneity in cancer and the search for new cancer-associated genes," Nature, Nature, vol. 499(7457), pages 214-218, July.
    7. Nighat Noureen & Shaofang Wu & Yingli Lv & Juechen Yang & W. K. Alfred Yung & Jonathan Gelfond & Xiaojing Wang & Dimpy Koul & Andrew Ludlow & Siyuan Zheng, 2021. "Integrated analysis of telomerase enzymatic activity unravels an association with cancer stemness and proliferation," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    8. Ludmil B. Alexandrov & Jaegil Kim & Nicholas J. Haradhvala & Mi Ni Huang & Alvin Wei Tian Ng & Yang Wu & Arnoud Boot & Kyle R. Covington & Dmitry A. Gordenin & Erik N. Bergstrom & S. M. Ashiqul Islam , 2020. "The repertoire of mutational signatures in human cancer," Nature, Nature, vol. 578(7793), pages 94-101, February.
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