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The mutational landscape of normal human endometrial epithelium
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Abstract
All normal somatic cells are thought to acquire mutations, but understanding of the rates, patterns, causes and consequences of somatic mutations in normal cells is limited. The uterine endometrium adopts multiple physiological states over a lifetime and is lined by a gland-forming epithelium1,2. Here, using whole-genome sequencing, we show that normal human endometrial glands are clonal cell populations with total mutation burdens that increase at about 29 base substitutions per year and that are many-fold lower than those of endometrial cancers. Normal endometrial glands frequently carry ‘driver’ mutations in cancer genes, the burden of which increases with age and decreases with parity. Cell clones with drivers often originate during the first decades of life and subsequently progressively colonize the epithelial lining of the endometrium. Our results show that mutational landscapes differ markedly between normal tissues—perhaps shaped by differences in their structure and physiology—and indicate that the procession of neoplastic change that leads to endometrial cancer is initiated early in life. Whole-genome sequencing of normal human endometrial glands shows that most are clonal cell populations and frequently carry cancer driver mutations that occur early in life, and that parity has a protective effect.
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“Taken together, these results demonstrate the significant advantage the toolkit we have developed in this study has to generate isogenic models of novel mutations in early tumorigenesis48,50–52.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [51]
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“While this hypothesis has been previously proposed48,50–52, it had never before been tested in an isogenic model.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [51]
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Citations
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
Fast and accurate long-read alignment with Burrows-Wheeler transform.
Li, H., & Durbin, R. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp698 · Cited by 12,063
Signatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660
Self-citationIntegrated genomic characterization of endometrial carcinoma
The Cancer Genome Atlas Research Network, & Levine, D. A. (2013) · Nature · doi:10.1038/nature12113 · Cited by 5,784
Age-related clonal hematopoiesis associated with adverse outcomes
Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., Lindsley, R. C., Mermel, C. H., Burtt, N., Chavez, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408617 · Cited by 4,841
Stratton, M. R., Campbell, P. J., & Futreal, P. A. (2009) · Nature · doi:10.1038/nature07943 · Cited by 3,625
Self-citationClonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence
Genovese, G., Kähler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., Chambert, K., Mick, E., Neale, B. M., Fromer, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409405 · Cited by 3,531
The repertoire of mutational signatures in human cancer
Alexandrov, L. B., Kim, J., Haradhvala, N. J., Huang, M. N., Tian Ng, A. W., Wu, Y., Boot, A., Covington, K. R., Gordenin, D. A., Bergstrom, E. N., et al. (2020) · Nature · doi:10.1038/s41586-020-1943-3 · Cited by 3,496
Self-citationYe, K., Schulz, M. H., Long, Q., Apweiler, R., & Ning, Z. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp394 · Cited by 2,029
Mutational Processes Molding the Genomes of 21 Breast Cancers
Nik-Zainal, S., Alexandrov, L. B., Wedge, D. C., Van Loo, P., Greenman, C. D., Raine, K., Jones, D., Hinton, J., Marshall, J., Stebbings, L. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.024 · Cited by 1,909
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Cited by
Sorted by citations
Items 101–200 of 499
Age-related somatic mutation burden in human tissues
Ren, P., Dong, X., & Vijg, J. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.1018119 · Cited by 58
Mutational landscape of normal epithelial cells in Lynch Syndrome patients
Lee, B. C. H., Robinson, P. S., Coorens, T. H. H., Yan, H. H. N., Ólafsson, S., Lee-Six, H., Sanders, M. A., Siu, H. C., Hewinson, J., Yue, S. S. K., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29920-2 · Cited by 51
Self-citationRates and Patterns of Clonal Oncogenic Mutations in the Normal Human Brain
Ganz, J., Maury, E. A., Becerra, B., Bizzotto, S., Doan, R. N., Kenny, C. J., Shin, T., Kim, J., Zhou, Z., Ligon, K. L., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0245 · Cited by 48
“Normal brain sSNVs statistically decomposed into several signatures (SBS 39, 5, 23, 1, 30, and 2), each reported in COSMIC as present in brain tumors (Fig.”
Genomic evidence of contemporary hybridization between Schistosoma species
Berger, D., Léger, E., Sankaranarayanan, G., Sène, M., Diouf, N. D., Rabone, M., Emery, A. M., Allan, F., Cotton, J. A., Berriman, M., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010706 · Cited by 50
How does the extent of fibrosis in adenomyosis lesions contribute to heavy menstrual bleeding?
Huang, Q., Liu, X., Critchley, H., Fu, Z., & Guo, S. (2022) · Reproductive Medicine and Biology · doi:10.1002/rmb2.12442 · Cited by 49
Murai, K., Dentro, S. C., Ong, S. H., Sood, R. K., Fernández‐Antorán, D., Herms, A., Kostiou, V., Abnizova, I., Hall, B. A., Gerstung, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33945-y · Cited by 52
Self-citationGenetic variation across and within individuals
Yu, Z., Coorens, T. H. H., Uddin, M. M., Ardlie, K., Lennon, N. J., & Natarajan, P. (2024) · Nature Reviews Genetics · doi:10.1038/s41576-024-00709-x · Cited by 51
“…isolating the clonal progeny of a single cell in vivo, often using laser capture microdissection 27,31,36,61 27 ; neurons 30,59 ; haematopoietic stem cells 32 ; stem cells of the bronchial 35 , endometrial 34 , colonic 31 and small intestinal 33 epithelium; and trophoblasts of the placenta 26”
BackgroundInfluentialSelf-citationMoukarzel, L. A., Paula, A. D. C., Ferrando, L., Hoang, T. J., Sebastião, A. P. M., Pareja, F. G., Park, K. J., Jungbluth, A. A., Capellá, G., Pineda, M., et al. (2020) · Modern Pathology · doi:10.1038/s41379-020-00721-6 · Cited by 49
SomaMutDB: a database of somatic mutations in normal human tissues
Sun, S., Wang, Y., Maslov, A. Y., Dong, X., & Vijg, J. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab914 · Cited by 50
Histopathologic diagnosis of endometrial precancers: Updates and future directions
Chen, H., Strickland, A. L., & Castrillón, D. H. (2021) · Seminars in Diagnostic Pathology · doi:10.1053/j.semdp.2021.12.001 · Cited by 47
Colorectal Cancer Is Associated with the Presence of Cancer Driver Mutations in Normal Colon
Matas, J., Kohrn, B., Fredrickson, J., Carter, K., Yu, M., Wang, T., Gui, X., Soussi, T., Moreno, V. R., Grady, W. M., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-21-3607 · Cited by 51
The long-term effects of chemotherapy on normal blood cells
Mitchell, E., Pham, M. H., Clay, A., Sanghvi, R., Williams, N., Pietsch, S., Hsu, J. I., Øbro, N. F., Jung, H., Vedi, A., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02234-x · Cited by 52
“WGS libraries were prepared from 1–5 ng of extracted DNA from each colony using a low-input enzymatic fragmentation-based library preparation method 48,49 .”
Self-citationLópez‐Janeiro, Á., Ruz‐Caracuel, I., Ramón-Patiño, J. L., Rı́os, V. D. L., Villalba-Esparza, M., Berjón, A., Yébenes, L., Hernández, A., Masetto, I., Kadioglu, E., et al. (2021) · Cancers · doi:10.3390/cancers13040794 · Cited by 46
A Revised Stem Cell Theory for the Pathogenesis of Endometriosis
Maruyama, T. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12020216 · Cited by 49
“CAMs can develop in glandular and/or luminal epithelial (stem/progenitor) cells of the eutopic endometrium, as suggested by the previous studies [60,63,66].”
BackgroundResultAddressing the benefits of inhibiting APOBEC3-dependent mutagenesis in cancer
Petljak, M., Green, A. M., Maciejowski, J., & Weitzman, M. D. (2022) · Nature Genetics · doi:10.1038/s41588-022-01196-8 · Cited by 46
Jakubek, Y. A., Chang, K., Sivakumar, S., Yu, Y., Giordano, M. R., Fowler, J., Huff, C., Kadara, H. N., Vilar, E., & Scheet, P. A. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0297-6 · Cited by 45
Fitness Landscape of Clonal Hematopoiesis Under Selective Pressure of Immune Checkpoint Blockade
Miller, P. G., Gibson, C. J., Mehta, A., Sperling, A. S., Frederick, D. T., Manos, M. P., Miao, B., Hacohen, N., Hodi, F. S., Boland, G. M., et al. (2020) · JCO Precision Oncology · doi:10.1200/po.20.00186 · Cited by 47
Rustad, E. H., Nadeu, F., Angelopoulos, N., Ziccheddu, B., Bolli, N., Puente, X. S., Campo, E., Landgren, O., & Maura, F. (2021) · Communications Biology · doi:10.1038/s42003-021-01938-0 · Cited by 42
Self-citationGenotoxic aldehydes in the hematopoietic system
Wang, M., Dingler, F. A., & Patel, K. J. (2022) · Blood · doi:10.1182/blood.2019004316 · Cited by 50
Development, maturation, and maintenance of human prostate inferred from somatic mutations
Großmann, S., Hooks, Y. E., Wilson, L., Moore, L., O’Neill, L., Martincorena, I., Voet, T., Stratton, M. R., Heer, R., & Campbell, P. J. (2021) · Cell stem cell · doi:10.1016/j.stem.2021.02.005 · Cited by 45
Self-citationEctopic Endometrium: The Pathologist’s Perspective
Camboni, A., & Marbaix, É. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222010974 · Cited by 46
Genomic Profiling of Bronchoalveolar Lavage Fluid in Lung Cancer
Nair, V. S., Hui, A. B., Chabon, J. J., Esfahani, M. S., Stehr, H., Nabet, B. Y., Zhou, L., Chaudhuri, A. A., Benson, J. A., Ayers, K., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-0554 · Cited by 45
The Dynamics of Somatic Mutagenesis During Life in Humans
Manders, F., van Boxtel, R., & Middelkamp, S. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.802407 · Cited by 48
Emerging diversity in extracellular vesicles and their roles in cancer
Sohal, I. S., & Kasinski, A. L. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1167717 · Cited by 44
HPV Meets APOBEC: New Players in Head and Neck Cancer
Riva, G., Albano, C., Gugliesi, F., Pasquero, S., Pacheco, S. F. C., Pecorari, G., Landolfo, S., Biolatti, M., & Dell’Oste, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031402 · Cited by 44
Yachida, N., Yoshihara, K., Yamaguchi, M., Suda, K., Tamura, R., & Enomoto, T. (2021) · Cancers · doi:10.3390/cancers13061439 · Cited by 48
Preneoplastic somatic mutations including MYD88 L265P in lymphoplasmacytic lymphoma
Rodríguez, S., Celay, J., Goicoechea, I., Jiménez, C., Botta, C., Garcia-Barchino, M. J., Garcés, J., Larráyoz, M., Santos, S. A., Alignani, D., et al. (2022) · Science Advances · doi:10.1126/sciadv.abl4644 · Cited by 47
Wang, M., Wu, Y., He, Y., Liu, J., Chen, Y., Huang, J., Qi, G., & Li, P. (2022) · Scientific Reports · doi:10.1038/s41598-022-16629-x · Cited by 43
Diniz-da-Costa, M., Kong, C., Fishwick, K. J., Rawlings, T. M., Brighton, P. J., Hawkes, A., Odendaal, J., Quenby, S. M., Ott, S., Lucas, E. S., et al. (2021) · Stem Cells · doi:10.1002/stem.3367 · Cited by 41
Self-citationSomatic variation in normal tissues: friend or foe of cancer early detection?
Acha‐Sagredo, A., Ganguli, P., & Ciccarelli, F. D. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.09.156 · Cited by 41
Normal breast tissues harbour rare populations of aneuploid epithelial cells
Lin, Y., Wang, J., Wang, K., Bai, S., Thennavan, A., Wei, R., Yan, Y., Li, J., Elgamal, H., Sei, E., et al. (2024) · Nature · doi:10.1038/s41586-024-08129-x · Cited by 44
Clonal hematopoiesis: Molecular and clinical implications
Kusne, Y. N., Xie, Z., & Patnaik, M. M. (2022) · Leukemia Research · doi:10.1016/j.leukres.2022.106787 · Cited by 43
Clonal dynamics and somatic evolution of haematopoiesis in mouse
Kapadia, C. D., Williams, N., Dawson, K. J., Watson, C. J., Yousefzadeh, M. J., Le, D. T., Nyamondo, K., Kodavali, S., Cagan, A., Waldvogel, S. M., et al. (2025) · Nature · doi:10.1038/s41586-025-08625-8 · Cited by 48
Self-citationThe Mutagenic Impact of Environmental Exposures in Human Cells and Cancer: Imprints Through Time
Huber, A. R., van Hoeck, A., & van Boxtel, R. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.760039 · Cited by 42
New Trends in the Detection of Gynecological Precancerous Lesions and Early-Stage Cancers
Holčáková, J., Bartošík, M., Anton, M., Minář, L., Hausnerová, J., Bednaříková, M., Weinberger, V., & Hrstka, R. (2021) · Cancers · doi:10.3390/cancers13246339 · Cited by 41
Somatic Mutation: What Shapes the Mutational Landscape of Normal Epithelia?
Fowler, J. C., & Jones, P. H. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0145 · Cited by 41
Temporal recording of mammalian development and precancer
Islam, M., Yang, Y., Simmons, A. J., Shah, V. M., Pavan, M. K., Xu, Y., Tasneem, N., Chen, Z., Trinh, L. T., Molina, P., et al. (2024) · Nature · doi:10.1038/s41586-024-07954-4 · Cited by 41
Prolonged persistence of mutagenic DNA lesions in somatic cells
Chapman, M. S., Mitchell, E., Yoshida, K., Williams, N., Fabre, M. A., Ranzoni, A. M., Robinson, P. S., Kregar, L. D., Wilk, C. M., Boettcher, S., et al. (2025) · Nature · doi:10.1038/s41586-024-08423-8 · Cited by 41
“Considering both these possibilities, we have tempered our wording in the main text (‘Timing and duration of persistent lesions’; p. 6) and in the legend to Figure 4, citing the additional references.”
Self-citationSperm sequencing reveals extensive positive selection in the male germline
Neville, M. D. C., Lawson, A. R. J., Sanghvi, R., Abascal, F., Pham, M. H., Cagan, A., Nicola, P. A., Bayzetinova, T., Baez‐Ortega, A., Roberts, K., et al. (2025) · Nature · doi:10.1038/s41586-025-09448-3 · Cited by 46
“Much higher burdens are seen in epithelial tissues such as endometrium, oesophagus and skin, where 30–50% of cells often have driver mutations 6,7,10 .”
Self-citationMultiomics insights into the female reproductive aging
Wei, S., Tang, W., Chen, D., Xiong, J., Xue, L., Dai, Y., Guo, Y., Wu, C., Dai, J., Wu, M., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102245 · Cited by 37
“In one study, utilizing WES, a total of 209 driver mutations were identified within the normal endometrial glands of 25 women (Moore et al., 2020).”
BackgroundJiang, M., Yang, Z., Dai, J., Wu, T., Jiao, Z., Yu, Y., Kang, N., Chen, W., & Yang, A. (2023) · MedComm · doi:10.1002/mco2.376 · Cited by 36
Decoding the basis of histological variation in human cancer
Fujii, M., Sekine, S., & Sato, T. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00648-5 · Cited by 35
Decoding and rejuvenating human ageing genomes: Lessons from mosaic chromosomal alterations
Dai, X., & Guo, X. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101342 · Cited by 39
Current Knowledge on Endometriosis Etiology: A Systematic Review of Literature
Михалева, Л. М., Radzinsky, V. E., Orazov, M. R., Николаевна, Х. Т., Sorokina, A. V., Александрович, М. С., Владимировна, В. С., Shustova, V. B., & Sinelnikov, M. Y. (2021) · International Journal of Women s Health · doi:10.2147/ijwh.s306135 · Cited by 37
Cell therapies in ovarian cancer
Sarivalasis, A., Morotti, M., Mulvey, A., Imbimbo, M., & Coukos, G. (2021) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359211008399 · Cited by 36
Molecular subversion of Cdc42 signalling in cancer
Murphy, N. P., Mokhtar, A. M. B. A., Mott, H. R., & Owen, D. (2021) · Biochemical Society Transactions · doi:10.1042/bst20200557 · Cited by 34
Marongiu, F., & DeGregori, J. V. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13275 · Cited by 38
Zhou, X., Yang, J., Lu, Y., Ma, Y., Meng, Y., Li, Q., Gao, J., Jiang, Z., Guo, L., Wang, W., et al. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04702-1 · Cited by 36
Organismal metabolism regulates the expansion of oncogenic PIK3CA mutant clones in normal esophagus
Herms, A., Colom, B., Piedrafita, G., Kalogeropoulou, A., Banerjee, U., King, C., Abby, E., Murai, K., Caseda, I., Fernández‐Antorán, D., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01891-8 · Cited by 33
Pathogenesis of bowel endometriosis
Yong, P. J., Bedaiwy, M. A., Alotaibi, F. T., & Anglesio, M. S. (2020) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2020.05.009 · Cited by 35
Cells with cancer‐associated mutations overtake our tissues as we age
Evans, E. J., & DeGregori, J. V. (2021) · Aging and Cancer · doi:10.1002/aac2.12037 · Cited by 35
Injectable 3D‐Printed Porous Scaffolds for Adipose Stem Cell Delivery and Endometrial Regeneration
Lü, S., Wang, X., Li, W., Zu, Y., & Xiao, J. (2023) · Advanced Functional Materials · doi:10.1002/adfm.202303368 · Cited by 33
Cancer‐associated mutations in normal human endometrium: Surprise or expected?
Kyo, S., Sato, S., & Nakayama, K. (2020) · Cancer Science · doi:10.1111/cas.14571 · Cited by 31
Biological significance of KRAS mutant allele expression in ovarian endometriosis
Yachida, N., Yoshihara, K., Suda, K., Nakaoka, H., Ueda, H., Sugino, K., Yamaguchi, M., Mori, Y., Yamawaki, K., Tamura, R., et al. (2021) · Cancer Science · doi:10.1111/cas.14871 · Cited by 32
Tovy, A., Reyes, J. M., Gundry, M. C., Brunetti, L., Lee-Six, H., Petljak, M., Park, H. J., Guzman, A. G., Rosas, C., Jeffries, A. R., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.06.018 · Cited by 30
Self-citationSingle-cell insights into epithelial morphogenesis in the neonatal mouse uterus
Spencer, T. E., Lowke, M. T., Davenport, K. M., Dhakal, P., & Kelleher, A. M. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2316410120 · Cited by 30
The role of host environment in cancer evolution
Solary, É., & Laplane, L. (2020) · Evolutionary Applications · doi:10.1111/eva.13039 · Cited by 33
Nikaido, M., Kakiuchi, N., Miyamoto, S., Hirano, T., Takeuchi, Y., Funakoshi, T., Yokoyama, A., Ogasawara, T., Yamamoto, Y., Yamada, A., et al. (2021) · Gastric Cancer · doi:10.1007/s10120-021-01191-8 · Cited by 29
Kabir, I., Zhang, X., Dave, J. M., Chakraborty, R., Qu, R., Chandran, R. R., Ntokou, A., Gallardo‐Vara, E., Aryal, B., Rotllán, N., et al. (2023) · Nature Aging · doi:10.1038/s43587-022-00342-5 · Cited by 29
A body map of somatic mutagenesis in morphologically normal human tissuesPreprint
Li, R., Di, L., Li, J., Fan, W., Liu, Y., Guo, W., Liu, W., Liu, L., Li, Q., Chen, L., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.30.403436 · Cited by 30
Carrami, E. M., Sharifzadeh, S., Wietek, N. C., Artibani, M., El-Sahhar, S., Sauka‐Spengler, T., Yau, C., Tresp, V., & Ahmed, A. A. (2020) · eLife · doi:10.7554/elife.55207 · Cited by 29
Epigenome Chaos: Stochastic and Deterministic DNA Methylation Events Drive Cancer Evolution
Russo, G., Tramontano, A., Iodice, I., Chiariotti, L., & Pezone, A. (2021) · Cancers · doi:10.3390/cancers13081800 · Cited by 30
Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women
Bartlett, T. E., Evans, I., Jones, A., Barrett, J. J. E., Haran, S. S., Reisel, D., Papaikonomou, K., Jones, J. L., Herzog, C. M. S., Pashayan, N., et al. (2022) · Genome Medicine · doi:10.1186/s13073-022-01063-5 · Cited by 27
An improved epigenetic counter to track mitotic age in normal and precancerous tissues
Zhu, T., Tong, H., Du, Z., Beck, S., & Teschendorff, A. E. (2024) · Nature Communications · doi:10.1038/s41467-024-48649-8 · Cited by 27
“Although recent studies have demonstrated a correlation of MS1 with chronological age in normal healthy tissue-types 52,80,81 , the analogous correlation of DNAm-based mitotic age with chronological age has been more widely demonstrated across many more normal tissue-types, including precancerous…”
Dynamic chromatin remodeling in cycling human endometrium at single-cell level
Vrljicak, P., Lucas, E. S., Tryfonos, M., Muter, J., Ott, S., & Brosens, J. J. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113525 · Cited by 30
Self-citationChemerinski, A., de Paredes, J. G., Blackledge, K. T., Douglas, N. C., & Morelli, S. S. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1332946 · Cited by 30
“A study of the somatic burden of endometrial glands of women aged 19 – 81 years found that approximately 29 base substitutions were added per gland per year, without a correlation to parity (Moore et al., 2020).”
BackgroundSomatic mutations in aging and disease
Ren, P., Zhang, J., & Vijg, J. (2024) · GeroScience · doi:10.1007/s11357-024-01113-3 · Cited by 30
“SBS18 is predominantly characterized by C > A substitutions and possibly due to reactive oxygen species [62].”
Aging promotes accumulation of senescent and multiciliated cells in human endometrial epithelium
Loid, M., Obukhova, D., Kask, K., Apostolov, A., Meltsov, A., Tserpelis, D., van den Wijngaard, A., Altmäe, S., Yahubyan, G. T., Baev, V., et al. (2024) · Human Reproduction Open · doi:10.1093/hropen/hoae048 · Cited by 31
“Moreover, genetic studies suggest that age increases the gene mutation burden in endometrial tissue, particularly in epithelial cells (Moore et al. , 2020), which could potentially alter endometrial function with respect to receptivity and implantation in both natural and assisted conception, and…”
BackgroundSmithgall, M. C., Remotti, H. E., Hsiao, S. J., et al. (2021) · Human Pathology · doi:10.1016/j.humpath.2021.10.004 · Cited by 28
The Genetic Evolution of Metastasis
Rogiers, A., Lobón, I., Spain, L. A., & Turajlic, S. (2022) · Cancer Research · doi:10.1158/0008-5472.can-21-3863 · Cited by 29
Havas, A. P., Yin, S., & Adams, P. D. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13302 · Cited by 32
Guo, S., Habiba, M. A., & Benagiano, G. (2023) · Biomolecules · doi:10.3390/biom13020336 · Cited by 30
Chronic Viral Mimicry Induction following p53 Loss Promotes Immune Evasion
Ishak, C. A., Marhon, S. A., Tchrakian, N., Hodgson, A., Yau, H. L., Gonzaga, I. M., Peralta, M., Lungu, I. M., Gomez, S., Liang, S., et al. (2025) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0094 · Cited by 28
Kostecka, A., Nowikiewicz, T., Olszewski, P., Koczkowska, M., Horbacz, M., Heinzl, M., Andreou, M., Salazar, R., Mair, T., Madanecki, P., et al. (2022) · npj Breast Cancer · doi:10.1038/s41523-022-00443-9 · Cited by 27
Somatic evolution in non-neoplastic IBD-affected colonPreprint
Ólafsson, S., McIntyre, R. E., Coorens, T. H. H., Butler, T. M., Jung, H., Robinson, P. S., Lee-Six, H., Sanders, M. A., Arestang, K., Dawson, C., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/832014 · Cited by 27
Self-citationCentini, G., Schettini, G., Pieri, E., Giorgi, M., Lazzeri, L., Martire, F. G., Mancini, V., Raimondo, D., Seracchioli, R., Habib, N., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13071933 · Cited by 27
Endometriosis and ovulatory menstruation: beyond the Sampson principle
Bulun, S. E. (2025) · Journal of Clinical Investigation · doi:10.1172/jci188787 · Cited by 29
“Although mutations sporadically affect small numbers of cells distributed across the eutopic endometrium, the majority of endo-metriotic epithelial cells carry these mutations in the same individual (21–25, 46, 86, 87).”
InfluentialLandgren, O. (2021) · Hematology · doi:10.1182/hematology.2021000303 · Cited by 30
Bowes, A. L., Tarabichi, M., Pillay, N., & Loo, P. V. (2022) · The Journal of Pathology · doi:10.1002/path.5914 · Cited by 29
Widespread chromatin context-dependencies of DNA double-strand break repair proteins
Vergara, X., Manjón, A. G., de Haas, M., Morris, B., Schep, R., Leemans, C., Friskes, A., Beijersbergen, R. L., Sanders, M. A., Medema, R. H., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49232-x · Cited by 26
“E Total MMEJ and NHEJ signature indel log 2 ratio in euchromatin (Eu.) and constitutive lamina-associatedheterochromatin(Het.)ingenomesoftumorswithindicatedgenotypes.”
InfluentialSelf-citationGermline genetic variation impacts clonal hematopoiesis landscape and progression to malignancy
Liu, J., Tran, D., Xue, L., Wiley, B. J., Vlasschaert, C., Watson, C. J., MacGregor, H. A. J., Zong, X., Chan, I. C. C., Das, I., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02250-x · Cited by 28
Unraveling the genomic landscape of colorectal cancer through mutational signatures
Díaz‐Gay, M., & Alexandrov, L. B. (2021) · Advances in cancer research · doi:10.1016/bs.acr.2021.03.003 · Cited by 28
Acquired Evolution of Mitochondrial Metabolism Regulated by HNF1B in Ovarian Clear Cell Carcinoma
Yamaguchi, K. D., Kitamura, S., Furutake, Y., Murakami, R., Yamanoi, K., Taki, M., Ukita, M., Hamanishi, J., & Mandai, M. (2021) · Cancers · doi:10.3390/cancers13102413 · Cited by 26
Genomic instability in early systemic sclerosis
Gniadecki, R., Iyer, A., Hennessey, D., Khan, L., O’Keefe, S. L., Redmond, D., Storek, J., Durand, C., Tervaert, J. W. C., & Osman, M. S. (2022) · Journal of Autoimmunity · doi:10.1016/j.jaut.2022.102847 · Cited by 26
Somatic mutations in human ageing: New insights from DNA sequencing and inherited mutations
Chatsirisupachai, K., & de Magalhães, J. P. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102268 · Cited by 27
The origin of hepatocellular carcinoma depends on metabolic zonation
Guo, J., Liang, R., Chung, A., Li, Z., Li, B., Chen, E., Li, L., Wang, J., Hsieh, M.-H., Fang, I. X., et al. (2026) · Science · doi:10.1126/science.adv7129 · Cited by 24
APOBEC Mutagenesis in Cancer Development and Susceptibility
Dananberg, A., Striepen, J., Rozowsky, J. S., & Petljak, M. (2024) · Cancers · doi:10.3390/cancers16020374 · Cited by 28
“[14,97]; however, they have not been identified in cells from respective healthy tissue types [32,76,77,90,91].”
BackgroundOn epigenetic stochasticity, entropy and cancer risk
Teschendorff, A. E. (2024) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2023.0054 · Cited by 24
Kobayashi, H., Imanaka, S., Yoshimoto, C., Matsubara, S., & Shigetomi, H. (2024) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.16089 · Cited by 26
“42 Other studies 45,46 also confirmed the presence of somatic driver mutations in normal endometrium.”
Tracking hematopoietic stem cells and their progeny using whole-genome sequencing
Lee-Six, H., & Kent, D. G. (2020) · Experimental Hematology · doi:10.1016/j.exphem.2020.01.004 · Cited by 26
Self-citationFrequent PIK3CA mutations in eutopic endometrium of patients with ovarian clear cell carcinoma
Murakami, K., Kanto, A., Sakai, K., Miyagawa, C., Takaya, H., Nakai, H., Kotani, Y., Nishio, K., & Matsumura, N. (2021) · Modern Pathology · doi:10.1038/s41379-021-00861-3 · Cited by 25
Molecular subversion of Cdc42 signalling in cancer.
Murphy, N. P., Mokhtar, A. M. A., Mott, H. R., & Owen, D. (2021) · Apollo (University of Cambridge) · doi:10.17863/cam.70501 · Cited by 24
Herms, A., Fernández‐Antorán, D., Alcolea, M. P., Kalogeropoulou, A., Banerjee, U., Piedrafita, G., Abby, E., Valverde-Lopez, J. A., Ferreira, I. S. D. S. R., Caseda, I., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01875-8 · Cited by 26
Self-citationLiu, T., Zhao, X., Lin, Y., Luo, Q., Zhang, S., Xi, Y., Chen, Y., Lin, L., Fan, W., Yang, J., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-0668 · Cited by 24
Fonseca-Montaño, M. A., Blancas, S., Herrera, L. A., & Hidalgo‐Miranda, A. (2022) · Archives of Medical Research · doi:10.1016/j.arcmed.2022.11.011 · Cited by 27
Rane, J. K., Frankell, A. M., Weeden, C. E., & Swanton, C. (2023) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-22-0469 · Cited by 25
“These include colonic crypts and endometrial glands, and post-mitotic tissues, such as neurons and smooth muscles (20,21,24,25,27,33,34,64).”
BackgroundInfluentialConvergent somatic evolution commences in utero in a germline ribosomopathy
Machado, H. E., Øbro, N. F., Williams, N., Tan, S., Boukerrou, A. Z., Davies, M., Belmonte, M., Mitchell, E., Baxter, E. J., Mende, N., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40896-5 · Cited by 25
“We removed artefacts from the SV calls using AnnotateBRASS (https://github.com/ MathijsSanders/AnnotateBRASS 66 ) with default settings.”
Self-citationAre Adenomyosis and Endometriosis Phenotypes of the Same Disease Process?
Habiba, M. A., Guo, S., & Benagiano, G. (2023) · Biomolecules · doi:10.3390/biom14010032 · Cited by 28
“Since endometrium from apparently could also harbor KRAS mutations, which confer proliferative advantage any overt pathology [89],we have Since endometrium from apparently healthy women could also harbor KRAS mutations, which confer proliferative advantage without causing any overt pathology [89],…”
BackgroundLife without mismatch repairPreprint
Sanders, M. A., Vöhringer, H. S., Forster, V. J., Moore, L., Campbell, B. B., Hooks, Y. E., Edwards, M., Bianchi, V., Coorens, T. H. H., Butler, T. M., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.14.437578 · Cited by 23
Self-citationGoldman, E. A., Spellman, P. T., & Agarwal, A. (2023) · Molecular Case Studies · doi:10.1101/mcs.a006251 · Cited by 25
“…to blood but occurs in many other tissues (e.g., skin, Martincorena et al. 2015; bronchus, Yoshida et al. 2020; endometrium, Suda et al. 2018, Moore et al. 2020; and esophagus, Martincorena et al. 2018), it has been best studied in the context of the hematopoietic system, in part because of…”
Metadata
- Authors
- Moore, L., Leongamornlert, D., Coorens, T. H. H., Sanders, M. A., Ellis, P., Dentro, S. C., Dawson, K. J., Butler, T., Rahbari, R., Mitchell, T. J., Maura, F., Nangalia, J., Tarpey, P. S., Brunner, S. F., Lee-Six, H., Hooks, Y., Moody, S., Mahbubani, K. T., Jimenez-Linan, M., Brosens, J. J., Iacobuzio-Donahue, C. A., Martincorena, I., Saeb-Parsy, K., Campbell, P. J., & Stratton, M. R.
- Affiliations
- Cambridge University Hospitals NHS Foundation Trust (GB)
- Wellcome Sanger Institute (GB)
- Erasmus MC (NL)
- European Bioinformatics Institute (GB)
- Memorial Sloan Kettering Cancer Center (US)
- University of Cambridge (GB)
- University of Warwick (GB)
- Corresponding author
- Stratton, Michael R.
- ORCID
- Moore, Luiza
- Leongamornlert, Daniel
- Coorens, Tim H. H.
- Sanders, Mathijs A.
- Dentro, Stefan C.
- Butler, Tim
- Rahbari, Raheleh
- Mitchell, Thomas J.
- Maura, Francesco
- Nangalia, Jyoti
- Tarpey, Patrick S.
- Lee-Six, Henry
- Moody, Sarah
- Mahbubani, Krishnaa T.
- Brosens, Jan J.
- Iacobuzio-Donahue, Christine A.
- Saeb-Parsy, Kourosh
- Campbell, Peter J.
- Stratton, Michael R.
- Venue
- Nature
- Published
- 2020-04-22
- Volume
- 580
- Issue
- 7805
- Pages
- 640-646
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3020114628
- Semantic Scholar
- 64bced314a97056c50b400d859c78993c4ce2fd8
- Cited by
- 499
- References
- 64
- Citations by year
- 2026: 42 · 2025: 54 · 2024: 69 · 2023: 87 · 2022: 91 · 2021: 89 · 2020: 51
- FWCI
- 27.19
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation
- European Hematology Association (TRTH182)
- Wellcome Trust (103858/Z/14/Z)
- Cancer Research UK (C20/A20917, 23917, 27176, 21777, 27114)
- Pathological Society of Great Britain and Ireland
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (171753, 180790)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (019.153LW.038)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- somatic mutations, endometrial epithelium, endometrial cancer, clonal cell populations, mutational burden, driver mutations, cancer genes, parity, aging, mutational landscape, tumor progression, endometrial glands
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Clone Cells, DNA Mutational Analysis, Endometrium, Epithelial Cells, Epithelium, Female, Health, Humans, Middle Aged, Mutation, Parity, Time Factors, Endometrial Neoplasms, Age of Onset, Young Adult, Carcinogenesis
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