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Parity associates with chromosomal damage in uterine leiomyomas

Author

Listed:
  • Heli Kuisma

    (Department of Medical and Clinical Genetics and Applied Tumor Genomics Research Program University of Helsinki)

  • Simona Bramante

    (Department of Medical and Clinical Genetics and Applied Tumor Genomics Research Program University of Helsinki)

  • Kristiina Rajamäki

    (Department of Medical and Clinical Genetics and Applied Tumor Genomics Research Program University of Helsinki)

  • Lauri J. Sipilä

    (Department of Medical and Clinical Genetics and Applied Tumor Genomics Research Program University of Helsinki)

  • Eevi Kaasinen

    (Department of Medical and Clinical Genetics and Applied Tumor Genomics Research Program University of Helsinki)

  • Jaana Kaukomaa

    (Department of Medical and Clinical Genetics and Applied Tumor Genomics Research Program University of Helsinki)

  • Kimmo Palin

    (Department of Medical and Clinical Genetics and Applied Tumor Genomics Research Program University of Helsinki)

  • Netta Mäkinen

    (Department of Medical and Clinical Genetics and Applied Tumor Genomics Research Program University of Helsinki)

  • Jari Sjöberg

    (University of Helsinki and Helsinki University Hospital)

  • Nanna Sarvilinna

    (University of Helsinki and Helsinki University Hospital
    University of Helsinki)

  • Jussi Taipale

    (Department of Medical and Clinical Genetics and Applied Tumor Genomics Research Program University of Helsinki)

  • Liisa Kauppi

    (University of Helsinki)

  • Manuela Tumiati

    (University of Helsinki)

  • Antti Hassinen

    (FIMM-HCA, Institute for Molecular Medicine Finland (FIMM))

  • Janne Pitkäniemi

    (Finnish Cancer Registry
    University of Tampere
    University of Helsinki)

  • Jyrki Jalkanen

    (Central Finland Central Hospital)

  • Sanna Heikkinen

    (Finnish Cancer Registry)

  • Annukka Pasanen

    (University of Helsinki and Helsinki University Hospital)

  • Oskari Heikinheimo

    (University of Helsinki and Helsinki University Hospital)

  • Ralf Bützow

    (University of Helsinki and Helsinki University Hospital)

  • Niko Välimäki

    (Department of Medical and Clinical Genetics and Applied Tumor Genomics Research Program University of Helsinki)

  • Lauri A. Aaltonen

    (Department of Medical and Clinical Genetics and Applied Tumor Genomics Research Program University of Helsinki)

Abstract

Mechanical forces in a constrained cellular environment were recently established as a facilitator of chromosomal damage. Whether this could contribute to tumorigenesis is not known. Uterine leiomyomas are common neoplasms that display relatively few chromosomal aberrations. We hypothesized that if mechanical forces contribute to chromosomal damage, signs of this could be seen in uterine leiomyomas from parous women. We examined the karyotypes of 1946 tumors, and found a striking overrepresentation of chromosomal damage associated with parity. We then subjected myometrial cells to physiological forces similar to those encountered during pregnancy, and found this to cause DNA breaks and a DNA repair response. While mechanical forces acting in constrained cellular environments may thus contribute to neoplastic degeneration, and genesis of uterine leiomyoma, further studies are needed to prove possible causality of the observed association. No evidence for progression to malignancy was found.

Suggested Citation

  • Heli Kuisma & Simona Bramante & Kristiina Rajamäki & Lauri J. Sipilä & Eevi Kaasinen & Jaana Kaukomaa & Kimmo Palin & Netta Mäkinen & Jari Sjöberg & Nanna Sarvilinna & Jussi Taipale & Liisa Kauppi & M, 2021. "Parity associates with chromosomal damage in uterine leiomyomas," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25806-x
    DOI: 10.1038/s41467-021-25806-x
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