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Molecular profiling of 888 pediatric tumors informs future precision trials and data-sharing initiatives in pediatric cancer

Author

Listed:
  • Suzanne J. Forrest

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

  • Hersh Gupta

    (Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard)

  • Abigail Ward

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

  • Yvonne Y. Li

    (Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard)

  • Duong Doan

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

  • Alyaa Al-Ibraheemi

    (Harvard Medical School
    Boston Children’s Hospital)

  • Sanda Alexandrescu

    (Harvard Medical School
    Boston Children’s Hospital)

  • Pratiti Bandopadhayay

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

  • Suzanne Shusterman

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

  • Elizabeth A. Mullen

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

  • Natalie B. Collins

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

  • Susan N. Chi

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

  • Karen D. Wright

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

  • Priti Kumari

    (Dana-Farber Cancer Institute)

  • Tali Mazor

    (Dana-Farber Cancer Institute)

  • Keith L. Ligon

    (Harvard Medical School
    Dana-Farber Cancer Institute
    Boston Children’s Hospital
    Brigham and Women’s Hospital)

  • Priyanka Shivdasani

    (Brigham and Women’s Hospital)

  • Monica Manam

    (Boston Children’s Hospital)

  • Laura E. MacConaill

    (Brigham and Women’s Hospital)

  • Evelina Ceca

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

  • Sidney N. Benich

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

  • Wendy B. London

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

  • Richard L. Schilsky

    (American Society of Clinical Oncology)

  • Suanna S. Bruinooge

    (American Society of Clinical Oncology)

  • Jaime M. Guidry Auvil

    (National Cancer Institute)

  • Ethan Cerami

    (Dana-Farber Cancer Institute)

  • Barrett J. Rollins

    (Harvard Medical School
    Dana-Farber Cancer Institute
    Brigham and Women’s Hospital)

  • Matthew L. Meyerson

    (Harvard Medical School
    Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard)

  • Neal I. Lindeman

    (Weill Cornell Medical College)

  • Bruce E. Johnson

    (Harvard Medical School
    Dana-Farber Cancer Institute
    Brigham and Women’s Hospital)

  • Andrew D. Cherniack

    (Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard)

  • Alanna J. Church

    (Harvard Medical School
    Boston Children’s Hospital)

  • Katherine A. Janeway

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

Abstract

To inform clinical trial design and real-world precision pediatric oncology practice, we classified diagnoses, assessed the landscape of mutations, and identified genomic variants matching trials in a large unselected institutional cohort of solid tumors patients sequenced at Dana-Farber / Boston Children’s Cancer and Blood Disorders Center. Tumors were sequenced with OncoPanel, a targeted next-generation DNA sequencing panel. Diagnoses were classified according to the International Classification of Diseases for Oncology (ICD-O-3.2). Over 6.5 years, 888 pediatric cancer patients with 95 distinct diagnoses had successful tumor sequencing. Overall, 33% (n = 289/888) of patients had at least 1 variant matching a precision oncology trial protocol, and 14% (41/289) were treated with molecularly targeted therapy. This study highlights opportunities to use genomic data from hospital-based sequencing performed either for research or clinical care to inform ongoing and future precision oncology clinical trials. Furthermore, the study results emphasize the importance of data sharing to define the genomic landscape and targeted treatment opportunities for the large group of rare pediatric cancers we encounter in clinical practice.

Suggested Citation

  • Suzanne J. Forrest & Hersh Gupta & Abigail Ward & Yvonne Y. Li & Duong Doan & Alyaa Al-Ibraheemi & Sanda Alexandrescu & Pratiti Bandopadhayay & Suzanne Shusterman & Elizabeth A. Mullen & Natalie B. Co, 2024. "Molecular profiling of 888 pediatric tumors informs future precision trials and data-sharing initiatives in pediatric cancer," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49944-0
    DOI: 10.1038/s41467-024-49944-0
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    References listed on IDEAS

    as
    1. Susanne N. Gröbner & Barbara C. Worst & Joachim Weischenfeldt & Ivo Buchhalter & Kortine Kleinheinz & Vasilisa A. Rudneva & Pascal D. Johann & Gnana Prakash Balasubramanian & Maia Segura-Wang & Sebast, 2018. "The landscape of genomic alterations across childhood cancers," Nature, Nature, vol. 555(7696), pages 321-327, March.
    2. 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.
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    Full references (including those not matched with items on IDEAS)

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