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Whole genome and transcriptome integrated analyses guide clinical care of pediatric poor prognosis cancers

Author

Listed:
  • Rebecca J. Deyell

    (BC Children’s Hospital and Research Institute)

  • Yaoqing Shen

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Emma Titmuss

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Katherine Dixon

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer
    University of British Columbia)

  • Laura M. Williamson

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Erin Pleasance

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Jessica M. T. Nelson

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Sanna Abbasi

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Martin Krzywinski

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Linlea Armstrong

    (University of British Columbia)

  • Melika Bonakdar

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Carolyn Ch’ng

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Eric Chuah

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Chris Dunham

    (University of British Columbia)

  • Alexandra Fok

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Martin Jones

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Anna F. Lee

    (University of British Columbia)

  • Yussanne Ma

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Richard A. Moore

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Andrew J. Mungall

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Karen L. Mungall

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Paul C. Rogers

    (BC Children’s Hospital and Research Institute)

  • Kasmintan A. Schrader

    (University of British Columbia)

  • Alice Virani

    (University of British Columbia)

  • Kathleen Wee

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Sean S. Young

    (University of British Columbia
    Department of Pathology and Laboratory Medicine, BC Cancer)

  • Yongjun Zhao

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer)

  • Steven J. M. Jones

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer
    University of British Columbia
    Simon Fraser University)

  • Janessa Laskin

    (BC Cancer)

  • Marco A. Marra

    (Canada’s Michael Smith Genome Sciences Centre at BC Cancer
    University of British Columbia)

  • Shahrad R. Rassekh

    (BC Children’s Hospital and Research Institute)

Abstract

The role for routine whole genome and transcriptome analysis (WGTA) for poor prognosis pediatric cancers remains undetermined. Here, we characterize somatic mutations, structural rearrangements, copy number variants, gene expression, immuno-profiles and germline cancer predisposition variants in children and adolescents with relapsed, refractory or poor prognosis malignancies who underwent somatic WGTA and matched germline sequencing. Seventy-nine participants with a median age at enrollment of 8.8 y (range 6 months to 21.2 y) are included. Germline pathogenic/likely pathogenic variants are identified in 12% of participants, of which 60% were not known prior. Therapeutically actionable variants are identified by targeted gene report and whole genome in 32% and 62% of participants, respectively, and increase to 96% after integrating transcriptome analyses. Thirty-two molecularly informed therapies are pursued in 28 participants with 54% achieving a clinical benefit rate; objective response or stable disease ≥6 months. Integrated WGTA identifies therapeutically actionable variants in almost all tumors and are directly translatable to clinical care of children with poor prognosis cancers.

Suggested Citation

  • Rebecca J. Deyell & Yaoqing Shen & Emma Titmuss & Katherine Dixon & Laura M. Williamson & Erin Pleasance & Jessica M. T. Nelson & Sanna Abbasi & Martin Krzywinski & Linlea Armstrong & Melika Bonakdar , 2024. "Whole genome and transcriptome integrated analyses guide clinical care of pediatric poor prognosis cancers," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48363-5
    DOI: 10.1038/s41467-024-48363-5
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    References listed on IDEAS

    as
    1. Konrad J. Karczewski & Laurent C. Francioli & Grace Tiao & Beryl B. Cummings & Jessica Alföldi & Qingbo Wang & Ryan L. Collins & Kristen M. Laricchia & Andrea Ganna & Daniel P. Birnbaum & Laura D. Gau, 2020. "The mutational constraint spectrum quantified from variation in 141,456 humans," Nature, Nature, vol. 581(7809), pages 434-443, May.
    2. Caralyn Reisle & Laura M. Williamson & Erin Pleasance & Anna Davies & Brayden Pellegrini & Dustin W. Bleile & Karen L. Mungall & Eric Chuah & Martin R. Jones & Yussanne Ma & Eleanor Lewis & Isaac Beck, 2022. "A platform for oncogenomic reporting and interpretation," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

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