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 BützowNiko Välimäki, Lauri A. Aaltonen

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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.

Original languageEnglish
Article number5448
JournalNature Communications
Issue number1
Publication statusPublished - 2021
Publication typeA1 Journal article-refereed

Publication forum classification

  • Publication forum level 3

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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