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Somatic mutations in 3929 HPV positive cervical cells associated with infection outcome and HPV type

Author

Listed:
  • Maisa Pinheiro

    (National Cancer Institute, National Institutes of Health)

  • Nicolas Wentzensen

    (National Cancer Institute, National Institutes of Health)

  • Michael Dean

    (National Cancer Institute, National Institutes of Health
    Leidos Biomedical Research, Inc.)

  • Meredith Yeager

    (National Cancer Institute, National Institutes of Health
    Leidos Biomedical Research, Inc.
    Hood College)

  • Zigui Chen

    (The Chinese University of Hong Kong)

  • Amulya Shastry

    (National Cancer Institute, National Institutes of Health
    Leidos Biomedical Research, Inc.)

  • Joseph F. Boland

    (National Cancer Institute, National Institutes of Health
    Leidos Biomedical Research, Inc.)

  • Sara Bass

    (National Cancer Institute, National Institutes of Health
    Leidos Biomedical Research, Inc.)

  • Laurie Burdett

    (National Cancer Institute, National Institutes of Health
    Leidos Biomedical Research, Inc.)

  • Thomas Lorey

    (Kaiser Permanente Northern California)

  • Sambit Mishra

    (National Cancer Institute, National Institutes of Health
    Leidos Biomedical Research, Inc.)

  • Philip E. Castle

    (National Cancer Institute, National Institutes of Health
    National Institutes of Health)

  • Mark Schiffman

    (National Cancer Institute, National Institutes of Health)

  • Robert D. Burk

    (Albert Einstein College of Medicine
    Albert Einstein College of Medicine)

  • Bin Zhu

    (National Cancer Institute, National Institutes of Health)

  • Lisa Mirabello

    (National Cancer Institute, National Institutes of Health)

Abstract

Invasive cervical cancers (ICC), caused by HPV infections, have a heterogeneous molecular landscape. We investigate the detection, timing, and HPV type specificity of somatic mutations in 3929 HPV-positive exfoliated cervical cell samples from individuals undergoing cervical screening in the U.S. using deep targeted sequencing in ICC cases, precancers, and HPV-positive controls. We discover a subset of hotspot mutations rare in controls (2.6%) but significantly more prevalent in precancers, particularly glandular precancer lesions (10.2%), and cancers (25.7%), supporting their involvement in ICC carcinogenesis. Hotspot mutations differ by HPV type, and HPV18/45-positive ICC are more likely to have multiple hotspot mutations compared to HPV16-positive ICC. The proportion of cells containing hotspot mutations is higher (i.e., higher variant allele fraction) in ICC and mutations are detectable up to 6 years prior to cancer diagnosis. Our findings demonstrate the feasibility of using exfoliated cervical cells for detection of somatic mutations as potential diagnostic biomarkers.

Suggested Citation

  • Maisa Pinheiro & Nicolas Wentzensen & Michael Dean & Meredith Yeager & Zigui Chen & Amulya Shastry & Joseph F. Boland & Sara Bass & Laurie Burdett & Thomas Lorey & Sambit Mishra & Philip E. Castle & M, 2024. "Somatic mutations in 3929 HPV positive cervical cells associated with infection outcome and HPV type," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51713-y
    DOI: 10.1038/s41467-024-51713-y
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    References listed on IDEAS

    as
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