Parity associates with chromosomal damage in uterine leiomyomas

Nat Commun. 2021 Sep 14;12(1):5448. doi: 10.1038/s41467-021-25806-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomechanical Phenomena
  • Chromosome Aberrations*
  • DNA Breaks, Double-Stranded
  • DNA Repair*
  • Female
  • Gene Expression
  • Humans
  • Hysterectomy
  • Karyotype
  • Leiomyoma / etiology
  • Leiomyoma / genetics*
  • Leiomyoma / pathology
  • Leiomyoma / surgery
  • Mediator Complex / genetics*
  • Mutation
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology
  • Myometrium / metabolism
  • Myometrium / pathology
  • Parity*
  • Pregnancy
  • Primary Cell Culture
  • Prospective Studies
  • Uterine Neoplasms / etiology
  • Uterine Neoplasms / genetics*
  • Uterine Neoplasms / pathology
  • Uterine Neoplasms / surgery

Substances

  • MED12 protein, human
  • Mediator Complex