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Comprehensive germline genomic profiles of children, adolescents and young adults with solid tumors

Author

Listed:
  • Sara Akhavanfard

    (Cleveland Clinic
    Case Western Reserve University)

  • Roshan Padmanabhan

    (Cleveland Clinic)

  • Lamis Yehia

    (Cleveland Clinic)

  • Feixiong Cheng

    (Cleveland Clinic
    Case Western Reserve University
    Case Western Reserve University School of Medicine)

  • Charis Eng

    (Cleveland Clinic
    Case Western Reserve University
    Case Western Reserve University School of Medicine
    Case Western Reserve University School of Medicine)

Abstract

Compared to adult carcinomas, there is a paucity of targeted treatments for solid tumors in children, adolescents, and young adults (C-AYA). The impact of germline genomic signatures has implications for heritability, but its impact on targeted therapies has not been fully appreciated. Performing variant-prioritization analysis on germline DNA of 1,507 C-AYA patients with solid tumors, we show 12% of these patients carrying germline pathogenic and/or likely pathogenic variants (P/LP) in known cancer-predisposing genes (KCPG). An additional 61% have germline pathogenic variants in non-KCPG genes, including PRKN, SMARCAL1, SMAD7, which we refer to as candidate genes. Despite germline variants in a broad gene spectrum, pathway analysis leads to top networks centering around p53. Our drug-target analysis shows 1/3 of patients with germline P/LP variants have at least one druggable alteration, while more than half of them are from our candidate gene group, which would otherwise go unidentified in routine clinical care.

Suggested Citation

  • Sara Akhavanfard & Roshan Padmanabhan & Lamis Yehia & Feixiong Cheng & Charis Eng, 2020. "Comprehensive germline genomic profiles of children, adolescents and young adults with solid tumors," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16067-1
    DOI: 10.1038/s41467-020-16067-1
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    Cited by:

    1. Xinyu Bai & Grace H. Attrill & Tuba N. Gide & Peter M. Ferguson & Kazi J. Nahar & Ping Shang & Ismael A. Vergara & Umaimainthan Palendira & Ines Pires Silva & Matteo S. Carlino & Alexander M. Menzies , 2024. "Stroma-infiltrating T cell spatiotypes define immunotherapy outcomes in adolescent and young adult patients with melanoma," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Eun Seop Seo & Ji Won Lee & Jinyeong Lim & Sunghwan Shin & Hee Won Cho & Hee Young Ju & Keon Hee Yoo & Ki Woong Sung & Woong-Yang Park, 2024. "Germline functional variants contribute to somatic mutation and outcomes in neuroblastoma," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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