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; Lauri A. Aaltonen

doi:10.1038/s41467-021-25806-x

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

Health Sciences

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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.

Original language	English
Article number	5448
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-25806-x
Publication status	Published - 2021
Publication type	A1 Journal article-refereed

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Publication forum level 3

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Kuisma, H., Bramante, S., Rajamäki, K., Sipilä, L. J., Kaasinen, E., Kaukomaa, J., Palin, K., Mäkinen, N., Sjöberg, J., Sarvilinna, N., Taipale, J., Kauppi, L., Tumiati, M., Hassinen, A., Pitkäniemi, J., Jalkanen, J., Heikkinen, S., Pasanen, A., Heikinheimo, O., ... Aaltonen, L. A. (2021). Parity associates with chromosomal damage in uterine leiomyomas. Nature Communications, 12(1), Article 5448. https://doi.org/10.1038/s41467-021-25806-x

@article{22621c3091dc4dbcba5e4e22fe9daec0,

title = "Parity associates with chromosomal damage in uterine leiomyomas",

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.",

author = "Heli Kuisma and Simona Bramante and Kristiina Rajam{\"a}ki and Sipil{\"a}, {Lauri J.} and Eevi Kaasinen and Jaana Kaukomaa and Kimmo Palin and Netta M{\"a}kinen and Jari Sj{\"o}berg and Nanna Sarvilinna and Jussi Taipale and Liisa Kauppi and Manuela Tumiati and Antti Hassinen and Janne Pitk{\"a}niemi and Jyrki Jalkanen and Sanna Heikkinen and Annukka Pasanen and Oskari Heikinheimo and Ralf B{\"u}tzow and Niko V{\"a}lim{\"a}ki and Aaltonen, {Lauri A.}",

note = "Funding Information: The study was supported by grants from the Academy of Finland (Finnish Center of Excellence No. 312041), European Research Council (ERC, 695727). N.M. received a grant from the Academy of Finland (295693) and Orion Research Foundation sr. L.K. is supported by the Academy of Finland (grant number 314394), the Sigrid Juselius Foundation and the Finnish Cancer Foundation. FIMM-HCA infrastructure is supported by Biocenter Finland. We acknowledge the computational resources provided by the ELIXIR node, hosted at the CSC-IT Center for Science Finland. We thank Prof. Eero Mervaala{\textquoteright}s laboratory for providing the cell stretching instrument and their expertize and guidance in using it. We are thankful to Sini Marttinen, Sirpa Soisalo, Marjo Rajalaakso, Inga-Lill {\AA}berg, Iina Vuoristo, Alison London, and Heikki Metsola for their technical assistance. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

doi = "10.1038/s41467-021-25806-x",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Kuisma, H, Bramante, S, Rajamäki, K, Sipilä, LJ, Kaasinen, E, Kaukomaa, J, Palin, K, Mäkinen, N, Sjöberg, J, Sarvilinna, N, Taipale, J, Kauppi, L, Tumiati, M, Hassinen, A, Pitkäniemi, J, Jalkanen, J, Heikkinen, S, Pasanen, A, Heikinheimo, O, Bützow, R, Välimäki, N & Aaltonen, LA 2021, 'Parity associates with chromosomal damage in uterine leiomyomas', Nature Communications, vol. 12, no. 1, 5448. https://doi.org/10.1038/s41467-021-25806-x

TY - JOUR

T1 - Parity associates with chromosomal damage in uterine leiomyomas

AU - Kuisma, Heli

AU - Bramante, Simona

AU - Rajamäki, Kristiina

AU - Sipilä, Lauri J.

AU - Kaasinen, Eevi

AU - Kaukomaa, Jaana

AU - Palin, Kimmo

AU - Mäkinen, Netta

AU - Sjöberg, Jari

AU - Sarvilinna, Nanna

AU - Taipale, Jussi

AU - Kauppi, Liisa

AU - Tumiati, Manuela

AU - Hassinen, Antti

AU - Pitkäniemi, Janne

AU - Jalkanen, Jyrki

AU - Heikkinen, Sanna

AU - Pasanen, Annukka

AU - Heikinheimo, Oskari

AU - Bützow, Ralf

AU - Välimäki, Niko

AU - Aaltonen, Lauri A.

N1 - Funding Information: The study was supported by grants from the Academy of Finland (Finnish Center of Excellence No. 312041), European Research Council (ERC, 695727). N.M. received a grant from the Academy of Finland (295693) and Orion Research Foundation sr. L.K. is supported by the Academy of Finland (grant number 314394), the Sigrid Juselius Foundation and the Finnish Cancer Foundation. FIMM-HCA infrastructure is supported by Biocenter Finland. We acknowledge the computational resources provided by the ELIXIR node, hosted at the CSC-IT Center for Science Finland. We thank Prof. Eero Mervaala’s laboratory for providing the cell stretching instrument and their expertize and guidance in using it. We are thankful to Sini Marttinen, Sirpa Soisalo, Marjo Rajalaakso, Inga-Lill Åberg, Iina Vuoristo, Alison London, and Heikki Metsola for their technical assistance. Publisher Copyright: © 2021, The Author(s).

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-021-25806-x

DO - 10.1038/s41467-021-25806-x

M3 - Article

AN - SCOPUS:85115275936

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5448

ER -

Parity associates with chromosomal damage in uterine leiomyomas

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