Parity associates with chromosomal damage in uterine leiomyomas

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, Manuela Tumiati, Antti Hassinen, Janne Pitkäniemi, Jyrki Jalkanen, Sanna Heikkinen, Annukka Pasanen, Oskari Heikinheimo, Ralf Bützow, Niko Välimäki and Lauri A. Aaltonen ()
Additional contact information
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
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
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

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-25806-x

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