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Spatiotemporal dynamics of clonal selection and diversification in normal endometrial epithelium

Author

Listed:
  • Manako Yamaguchi

    (Niigata University Graduate School of Medical and Dental Sciences)

  • Hirofumi Nakaoka

    (National Institute of Genetics
    Sasaki Foundation)

  • Kazuaki Suda

    (Niigata University Graduate School of Medical and Dental Sciences)

  • Kosuke Yoshihara

    (Niigata University Graduate School of Medical and Dental Sciences)

  • Tatsuya Ishiguro

    (Niigata University Graduate School of Medical and Dental Sciences)

  • Nozomi Yachida

    (Niigata University Graduate School of Medical and Dental Sciences)

  • Kyota Saito

    (Niigata University Graduate School of Medical and Dental Sciences)

  • Haruka Ueda

    (Niigata University Graduate School of Medical and Dental Sciences)

  • Kentaro Sugino

    (Niigata University Graduate School of Medical and Dental Sciences)

  • Yutaro Mori

    (Niigata University Graduate School of Medical and Dental Sciences)

  • Kaoru Yamawaki

    (Niigata University Graduate School of Medical and Dental Sciences)

  • Ryo Tamura

    (Niigata University Graduate School of Medical and Dental Sciences)

  • Sundaramoorthy Revathidevi

    (National Institute of Genetics)

  • Teiichi Motoyama

    (Niigata University Graduate School of Medical and Dental Sciences)

  • Kazuki Tainaka

    (Niigata University
    RIKEN Center for Biosystems Dynamics Research)

  • Roel G. W. Verhaak

    (The Jackson Laboratory for Genomic Medicine
    VU University Medical Center (VUmc))

  • Ituro Inoue

    (National Institute of Genetics)

  • Takayuki Enomoto

    (Niigata University Graduate School of Medical and Dental Sciences)

Abstract

It has become evident that somatic mutations in cancer-associated genes accumulate in the normal endometrium, but spatiotemporal understanding of the evolution and expansion of mutant clones is limited. To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-associated genes in the normal endometrium, we sequence 1311 endometrial glands from 37 women. By collecting endometrial glands from different parts of the endometrium, we show that multiple glands with the same somatic mutations occupy substantial areas of the endometrium. We demonstrate that “rhizome structures”, in which the basal glands run horizontally along the muscular layer and multiple vertical glands rise from the basal gland, originate from the same ancestral clone. Moreover, mutant clones detected in the vertical glands diversify by acquiring additional mutations. These results suggest that clonal expansions through the rhizome structures are involved in the mechanism by which mutant clones extend their territories. Furthermore, we show clonal expansions and copy neutral loss-of-heterozygosity events occur early in life, suggesting such events can be tolerated many years in the normal endometrium. Our results of the evolutionary dynamics of mutant clones in the human endometrium will lead to a better understanding of the mechanisms of endometrial regeneration during the menstrual cycle and the development of therapies for the prevention and treatment of endometrium-related diseases.

Suggested Citation

  • Manako Yamaguchi & Hirofumi Nakaoka & Kazuaki Suda & Kosuke Yoshihara & Tatsuya Ishiguro & Nozomi Yachida & Kyota Saito & Haruka Ueda & Kentaro Sugino & Yutaro Mori & Kaoru Yamawaki & Ryo Tamura & Sun, 2022. "Spatiotemporal dynamics of clonal selection and diversification in normal endometrial epithelium," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28568-2
    DOI: 10.1038/s41467-022-28568-2
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    as
    1. Henry Lee-Six & Sigurgeir Olafsson & Peter Ellis & Robert J. Osborne & Mathijs A. Sanders & Luiza Moore & Nikitas Georgakopoulos & Franco Torrente & Ayesha Noorani & Martin Goddard & Philip Robinson &, 2019. "The landscape of somatic mutation in normal colorectal epithelial cells," Nature, Nature, vol. 574(7779), pages 532-537, October.
    2. Swapan Mallick & Heng Li & Mark Lipson & Iain Mathieson & Melissa Gymrek & Fernando Racimo & Mengyao Zhao & Niru Chennagiri & Susanne Nordenfelt & Arti Tandon & Pontus Skoglund & Iosif Lazaridis & Sri, 2016. "The Simons Genome Diversity Project: 300 genomes from 142 diverse populations," Nature, Nature, vol. 538(7624), pages 201-206, October.
    3. Luiza Moore & Daniel Leongamornlert & Tim H. H. Coorens & Mathijs A. Sanders & Peter Ellis & Stefan C. Dentro & Kevin J. Dawson & Tim Butler & Raheleh Rahbari & Thomas J. Mitchell & Francesco Maura & , 2020. "The mutational landscape of normal human endometrial epithelium," Nature, Nature, vol. 580(7805), pages 640-646, April.
    4. Michael R. Stratton & Peter J. Campbell & P. Andrew Futreal, 2009. "The cancer genome," Nature, Nature, vol. 458(7239), pages 719-724, April.
    5. Konrad J. Karczewski & Laurent C. Francioli & Grace Tiao & Beryl B. Cummings & Jessica Alföldi & Qingbo Wang & Ryan L. Collins & Kristen M. Laricchia & Andrea Ganna & Daniel P. Birnbaum & Laura D. Gau, 2020. "The mutational constraint spectrum quantified from variation in 141,456 humans," Nature, Nature, vol. 581(7809), pages 434-443, May.
    6. Satoshi Inoue & Yasushi Hirota & Toshihide Ueno & Yamato Fukui & Emiko Yoshida & Takuo Hayashi & Shinya Kojima & Reina Takeyama & Taiki Hashimoto & Tohru Kiyono & Masako Ikemura & Ayumi Taguchi & Tomo, 2019. "Uterine adenomyosis is an oligoclonal disorder associated with KRAS mutations," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    7. Francesco Maura & Andrea Degasperi & Ferran Nadeu & Daniel Leongamornlert & Helen Davies & Luiza Moore & Romina Royo & Bachisio Ziccheddu & Xose S. Puente & Herve Avet-Loiseau & Peter J. Campbell & Se, 2019. "Author Correction: A practical guide for mutational signature analysis in hematological malignancies," Nature Communications, Nature, vol. 10(1), pages 1-1, December.
    8. Simon F. Brunner & Nicola D. Roberts & Luke A. Wylie & Luiza Moore & Sarah J. Aitken & Susan E. Davies & Mathijs A. Sanders & Pete Ellis & Chris Alder & Yvette Hooks & Federico Abascal & Michael R. St, 2019. "Somatic mutations and clonal dynamics in healthy and cirrhotic human liver," Nature, Nature, vol. 574(7779), pages 538-542, October.
    9. Michael S. Lawrence & Petar Stojanov & Craig H. Mermel & James T. Robinson & Levi A. Garraway & Todd R. Golub & Matthew Meyerson & Stacey B. Gabriel & Eric S. Lander & Gad Getz, 2014. "Discovery and saturation analysis of cancer genes across 21 tumour types," Nature, Nature, vol. 505(7484), pages 495-501, January.
    10. Nobuyuki Kakiuchi & Kenichi Yoshida & Motoi Uchino & Takako Kihara & Kotaro Akaki & Yoshikage Inoue & Kenji Kawada & Satoshi Nagayama & Akira Yokoyama & Shuji Yamamoto & Minoru Matsuura & Takahiro Hor, 2020. "Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis," Nature, Nature, vol. 577(7789), pages 260-265, January.
    11. Akira Yokoyama & Nobuyuki Kakiuchi & Tetsuichi Yoshizato & Yasuhito Nannya & Hiromichi Suzuki & Yasuhide Takeuchi & Yusuke Shiozawa & Yusuke Sato & Kosuke Aoki & Soo Ki Kim & Yoichi Fujii & Kenichi Yo, 2019. "Age-related remodelling of oesophageal epithelia by mutated cancer drivers," Nature, Nature, vol. 565(7739), pages 312-317, January.
    12. Francesco Maura & Andrea Degasperi & Ferran Nadeu & Daniel Leongamornlert & Helen Davies & Luiza Moore & Romina Royo & Bachisio Ziccheddu & Xose S. Puente & Herve Avet-Loiseau & Peter J. Campbell & Se, 2019. "A practical guide for mutational signature analysis in hematological malignancies," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    13. Kenichi Yoshida & Kate H. C. Gowers & Henry Lee-Six & Deepak P. Chandrasekharan & Tim Coorens & Elizabeth F. Maughan & Kathryn Beal & Andrew Menzies & Fraser R. Millar & Elizabeth Anderson & Sarah E. , 2020. "Tobacco smoking and somatic mutations in human bronchial epithelium," Nature, Nature, vol. 578(7794), pages 266-272, February.
    14. Ludmil B. Alexandrov & Jaegil Kim & Nicholas J. Haradhvala & Mi Ni Huang & Alvin Wei Tian Ng & Yang Wu & Arnoud Boot & Kyle R. Covington & Dmitry A. Gordenin & Erik N. Bergstrom & S. M. Ashiqul Islam , 2020. "The repertoire of mutational signatures in human cancer," Nature, Nature, vol. 578(7793), pages 94-101, February.
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