4.8 Article

Parity associates with chromosomal damage in uterine leiomyomas

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NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41467-021-25806-x

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资金

  1. Academy of Finland (Finnish Center of Excellence) [312041]
  2. European Research Council (ERC) [695727]
  3. Orion Research Foundation
  4. Sigrid Juselius Foundation
  5. Finnish Cancer Foundation
  6. Biocenter Finland
  7. Academy of Finland [295693, 314394]
  8. European Research Council (ERC) [695727] Funding Source: European Research Council (ERC)
  9. Academy of Finland (AKA) [295693, 314394, 295693, 314394] Funding Source: Academy of Finland (AKA)

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This study reveals an association between parity and chromosomal damage in uterine leiomyomas, suggesting that mechanical forces in a constrained cellular environment may contribute to tumor development without evidence of progression to malignancy.
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. Many factors have been associated with chromosomal damage, including mechanical forces in a constrained cellular environment. Here the authors reveal an association between parity and chromosomal damage by analysing karyotypes of 1946 uterine leiomyomas.

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