The DOI matches its Crossref record; 41 of the 42 references it cites were found in a registry or an index.
Age-related remodelling of oesophageal epithelia by mutated cancer drivers
Abstract
Clonal expansion in aged normal tissues has been implicated in the development of cancer. However, the chronology and risk dependence of the expansion are poorly understood. Here we intensively sequence 682 micro-scale oesophageal samples and show, in physiologically normal oesophageal epithelia, the progressive age-related expansion of clones that carry mutations in driver genes (predominantly NOTCH1), which is substantially accelerated by alcohol consumption and by smoking. Driver-mutated clones emerge multifocally from early childhood and increase their number and size with ageing, and ultimately replace almost the entire oesophageal epithelium in the extremely elderly. Compared with mutations in oesophageal cancer, there is a marked overrepresentation of NOTCH1 and PPM1D mutations in physiologically normal oesophageal epithelia; these mutations can be acquired before late adolescence (as early as early infancy) and significantly increase in number with heavy smoking and drinking. The remodelling of the oesophageal epithelium by driver-mutated clones is an inevitable consequence of normal ageing, which-depending on lifestyle risks-may affect cancer development.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Instead, the discovery of widespread clonal expansions in ageing human tissues19,50–52 raises the possibility that some somatic mutations contribute to ageing by driving clonal expansions of functionally altered cells at a cost to the organism49,53,54.”
From Somatic mutation rates scale with lifespan across mammals (2022) · cites this paper as [52]
In the citing paper
“An equivalent state is also pervasive in the epithelium of skin 14 and esophagus 15,16, suggesting that somatic mutation-driven clonal expansions may be a characteristic of aging in several tissues.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [16]
Citations
Cites
Conducting Meta-Analyses in R with the metafor Package
Viechtbauer, W. (2010) · Journal of Statistical Software · doi:10.18637/jss.v036.i03 · Cited by 20,464
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
Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration
Thorvaldsdottir, H., Robinson, J. T., & Mesirov, J. P. (2013) · Briefings in Bioinformatics · doi:10.1093/bib/bbs017 · Cited by 9,049
Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
Gerlinger, M., Rowan, A. J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., Martinez, P., Matthews, N., Stewart, A., Tarpey, P., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1113205 · Cited by 7,774
Mutational heterogeneity in cancer and the search for new cancer-associated genes
Lawrence, M. S., Stojanov, P., Polak, P., Kryukov, G. V., Cibulskis, K., Sivachenko, A., Carter, S. L., Stewart, C., Mermel, C. H., Roberts, S. A., et al. (2013) · Nature · doi:10.1038/nature12213 · Cited by 5,461
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
Clonal 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
Mermel, C. H., Schumacher, S. E., Hill, B., Meyerson, M. M., Beroukhim, R., & Getz, G. A. (2011) · Genome biology · doi:10.1186/gb-2011-12-4-r41 · Cited by 3,520
Greaves, M., & Maley, C. C. (2012) · Nature · doi:10.1038/nature10762 · Cited by 3,162
Clonal heterogeneity and tumor evolution: past, present, and the future
McGranahan, N., & Swanton, C. (2017) · Cell · doi:10.1016/j.cell.2017.01.018 · Cited by 2,840
Research works printed but not linked: 1
- Blokzijl, F., Janssen, R., Van Boxtel, R. & Cuppen, E. MutationalPatterns: an integrative R package for studying patterns in base substitution catalogues. Preprint at https://www.biorxiv.org/content/early/2016/08/30/071761 (2016).
Cited by
Sorted by citations
Pluripotent Stem Cell-Based Cell Therapy—Promise and Challenges
Yamanaka, S. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.09.014 · Cited by 1,268
Clonal hematopoiesis in human aging and disease
Jaiswal, S., & Ebert, B. L. (2019) · Science · doi:10.1126/science.aan4673 · Cited by 1,156
The evolutionary history of 2,658 cancers
Gerstung, M., Jolly, C., Leshchiner, I., Dentro, S. C., Gonzalez, S., Rosebrock, D., Mitchell, T. J., Rubanova, Y., Anur, P., Yu, K., et al. (2020) · Nature · doi:10.1038/s41586-019-1907-7 · Cited by 1,057
p53: 800 million years of evolution and 40 years of discovery
Levine, A. J. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0262-1 · Cited by 876
Lung adenocarcinoma promotion by air pollutants
Hill, W., Lim, E. L., Weeden, C. E., Lee, C., Augustine, M., Chen, K., Kuan, F.-C., Marongiu, F., Evans, E. J., Moore, D. A., et al. (2023) · Nature · doi:10.1038/s41586-023-05874-3 · Cited by 808
Cancer therapy shapes the fitness landscape of clonal hematopoiesis
Bolton, K. L., Ptashkin, R. N., Gao, T., Braunstein, L., Devlin, S. M., Kelly, D., Patel, M., Berthon, A., Syed, A., Yabe, M., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-00710-0 · Cited by 751
“This ratio was chosen based on minimizing sensitivity and specificity of CH calls through simulations of leukocyte contamination in the tumor (see Supplementary Notes and Supplementary Figures 11 and 12).”
Embracing cancer complexity: Hallmarks of systemic disease
Swanton, C., Bernard, E., Abbosh, C., André, F., Auwerx, J. H., Balmain, A., Bar‐Sagi, D., Bernards, R., Bullman, S., DeGregori, J. V., et al. (2024) · Cell · doi:10.1016/j.cell.2024.02.009 · Cited by 578
Tobacco smoking and somatic mutations in human bronchial epithelium
Yoshida, K., Gowers, K. H. C., Lee-Six, H., Chandrasekharan, D. P., Coorens, T. H. H., Maughan, E. F., Beal, K. M., Menzies, A. H., Millar, F. R., Anderson, E. L., et al. (2020) · Nature · doi:10.1038/s41586-020-1961-1 · Cited by 545
Clonal dynamics of haematopoiesis across the human lifespan
Mitchell, E., Chapman, M. S., Williams, N., Dawson, K. J., Mende, N., Calderbank, E. F., Jung, H., Mitchell, T. J., Coorens, T. H. H., Spencer, D. H., et al. (2022) · Nature · doi:10.1038/s41586-022-04786-y · Cited by 538
López-Otín, C., & Kroemer, G. (2021) · Cell · doi:10.1016/j.cell.2020.11.034 · Cited by 499
The mutational landscape of normal human endometrial epithelium
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., et al. (2020) · Nature · doi:10.1038/s41586-020-2214-z · Cited by 499
Somatic mutation rates scale with lifespan across mammals
Cagan, A., Baez-Ortega, A., Brzozowska, N., Abascal, F., Coorens, T. H. H., Sanders, M. A., Lawson, A. R. J., Harvey, L. M. R., Bhosle, S., Jones, D., et al. (2022) · Nature · doi:10.1038/s41586-022-04618-z · Cited by 481
The future of early cancer detection
Fitzgerald, R. C., Antoniou, A. C., Fruk, L., & Rosenfeld, N. (2022) · Nature Medicine · doi:10.1038/s41591-022-01746-x · Cited by 486
“These include: (1) clinically meaningful abnormalities, not incidental findings, must be identified; (2) treatment must be available that is as minimally invasive or as minimally toxic as possible; (3) testing needs to reach those individuals who could benefit most, including disadvantaged groups who may not seek heal…”
BackgroundThe evolutionary dynamics and fitness landscape of clonal hematopoiesis
Watson, C. J., Papula, A. L., Poon, G. Y. P., Wong, W. H., Young, A. L., Druley, T. E., Fisher, D. S., & Blundell, J. R. (2020) · Science · doi:10.1126/science.aay9333 · Cited by 444
Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets
Zhang, S., Xiao, X., Yi, Y., Wang, X., Zhu, L., Shen, Y., Lin, D., & Wu, C. H. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01848-7 · Cited by 463
“160,161 In the tumor initiating stage, chemical and radical carcinogens not only induce mutations and contribute to speci fi c mutational signatures, 54,162 but also promote clonal expansion of speci fi c mutations.”
BackgroundSomatic mutations and clonal dynamics in healthy and cirrhotic human liver
Brunner, S. F., Roberts, N. D., Wylie, L. A., Moore, L., Aitken, S. J., Davies, S. E., Sanders, M. A., Ellis, P., Alder, C., Hooks, Y., et al. (2019) · Nature · doi:10.1038/s41586-019-1670-9 · Cited by 393
YAP and TAZ: a signalling hub of the tumour microenvironment
Zanconato, F., Cordenonsi, M., & Piccolo, S. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0168-y · Cited by 388
Integrating genetic and non-genetic determinants of cancer evolution by single-cell multi-omics
Nam, A. S., Chaligné, R., & Landau, D. A. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-0265-5 · Cited by 399
The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic
Kadosh, E., Snir-Alkalay, I., Venkatachalam, A., May, S., Lasry, A., Elyada, E., Zinger, A., Shaham, M., Vaalani, G., Mernberger, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2541-0 · Cited by 378
Melzer, D. R., Pilling, L. C., & Ferrucci, L. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0183-6 · Cited by 387
Dissecting Esophageal Squamous-Cell Carcinoma Ecosystem by Single-Cell Transcriptomic Analysis
Zhang, X., Peng, L., Luo, Y., Zhang, S., Pu, Y., Chen, Y., Guo, W., Yao, J., Shao, M., Fan, W., et al. (2020) · Nature Communications · doi:10.1038/s41467-021-25539-x · Cited by 385
Cancer as a disease of old age: changing mutational and microenvironmental landscapes
Laconi, E., Marongiu, F., & DeGregori, J. (2020) · British Journal of Cancer · doi:10.1038/s41416-019-0721-1 · Cited by 348
“The nature of the selective environment is crucial to the genotype/phenotype of the clone that emerges, as one would expect.(85) In the haematopoietic system, age-related clonal expansions involving TP53 and spliceosome genes are predictive of the later development of acute myeloid leukaemia,(103) and clones with TP53…”
BackgroundSomatic inflammatory gene mutations in human ulcerative colitis epithelium
Nanki, K., Fujii, M., Shimokawa, M., Matano, M., Nishikori, S., Date, S., Takano, A., Toshimitsu, K., Ohta, Y., Takahashi, S., et al. (2019) · Nature · doi:10.1038/s41586-019-1844-5 · Cited by 333
Extensive heterogeneity in somatic mutation and selection in the human bladder
Lawson, A. R. J., Abascal, F., Coorens, T. H. H., Hooks, Y., O’Neill, L., Latimer, C., Raine, K., Sanders, M. A., Warren, A. Y., Mahbubani, K. T. A., et al. (2020) · Science · doi:10.1126/science.aba8347 · Cited by 311
Accumulation of genetic and epigenetic alterations in normal cells and cancer risk
Takeshima, H., & Ushijima, T. (2019) · npj Precision Oncology · doi:10.1038/s41698-019-0079-0 · Cited by 321
“In normal esophageal tissues, NOTCH1 mutations were present in 25–42% of the cells, and were considered to be associated with clonal expansion.(18,19) In benign lesions of melanoma patients, which are clearly with clonal expansion, BRAF V600E mutation was detected.”
BackgroundMethodInflammation-Induced Tumorigenesis and Metastasis
Hibino, S., Kawazoe, T., Kasahara, H., Itoh, S., Ishimoto, T., Sakata‐Yanagimoto, M., & Taniguchi, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115421 · Cited by 319
Mutational signatures: emerging concepts, caveats and clinical applications
Koh, C. C., Degasperi, A., Zou, X., Momen, S., & Nik‐Zainal, S. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00377-7 · Cited by 291
Life histories of myeloproliferative neoplasms inferred from phylogenies
Williams, N., Lee, J., Mitchell, E., Moore, L., Baxter, E. J., Hewinson, J., Dawson, K. J., Menzies, A., Godfrey, A. L., Green, A. R., et al. (2022) · Nature · doi:10.1038/s41586-021-04312-6 · Cited by 285
Zhou, Y., Bian, S., Zhou, X., Cui, Y., Wang, W., Wen, L., Guo, L., Fu, W., & Tang, F. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.09.015 · Cited by 278
Targeting Notch in oncology: the path forward
Majumder, S., Crabtree, J. S., Golde, T. E., Minter, L. M., Osborne, B. A., & Miele, L. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-00091-3 · Cited by 279
Clonal expansion in non-cancer tissues
Kakiuchi, N., & Ogawa, S. (2021) · Nature Reviews Cancer · doi:10.1038/s41568-021-00335-3 · Cited by 252
Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis
Kakiuchi, N., Yoshida, K., Uchino, M., Kihara, T., Akaki, K., Inoue, Y., Kawada, K., Nagayama, S., Yokoyama, A., Yamamoto, S., et al. (2019) · Nature · doi:10.1038/s41586-019-1856-1 · Cited by 262
Imperfect wound healing sets the stage for chronic diseases
Martin, P. B., Pardo-Pastor, C., Jenkins, G. R., & Rosenblatt, J. (2024) · Science · doi:10.1126/science.adp2974 · Cited by 262
“Second, oncogenic mutations are routinely found in healthy tissues and benign tumors, accumulating with age in the absence of cancer (94–98).”
Somatic Mutations Increase Hepatic Clonal Fitness and Regeneration in Chronic Liver Disease
Zhu, M., Lu, T., Jia, Y., Luo, X., Gopal, P., Li, L., Odewole, M., Renteria, V., Singal, A. G., Jang, Y., et al. (2019) · Cell · doi:10.1016/j.cell.2019.03.026 · Cited by 250
“, 2015) and the esophagi of over 100 individuals (Martincorena et al., 2018; Yokoyama et al., 2019).”
Advances in diagnosis and management of cancer of the esophagus
Deboever, N., Jones, C. M., Yamashita, K., Ajani, J. A., & Hofstetter, W. L. (2024) · BMJ · doi:10.1136/bmj-2023-074962 · Cited by 275
“12 13 This remodeling can be catalyzed by exogenous exposures, such as alcohol consumption and smoking, eventually reaching between 9000 and 15 000 clones per esophagus.”
BackgroundYAP/TAZ as master regulators in cancer: modulation, function and therapeutic approaches
Piccolo, S., Panciera, T., Contessotto, P., & Cordenonsi, M. (2022) · Nature Cancer · doi:10.1038/s43018-022-00473-z · Cited by 264
Update on Management of Squamous Cell Esophageal Cancer
Waters, J. K., & Reznik, S. I. (2022) · Current Oncology Reports · doi:10.1007/s11912-021-01153-4 · Cited by 242
Pathogenic mechanisms of somatic mutation and genome mosaicism in aging
Vijg, J., & Dong, X. (2020) · Cell · doi:10.1016/j.cell.2020.06.024 · Cited by 240
“Similar results were obtained by Yokoyama et al (Yokoyama et al., 2019).”
ResultTracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma
Lee, J. J.-K., Park, S., Park, H., Kim, S., Lee, J., Lee, J., Youk, J., Yi, K., An, Y., Park, I. K., et al. (2019) · Cell · doi:10.1016/j.cell.2019.05.013 · Cited by 233
Self-citationPanciera, T., Citron, A., Biagio, D. D., Battilana, G., Gandin, A., Giulitti, S., Forcato, M., Bicciato, S., Panzetta, V., Fusco, S., et al. (2020) · Nature Materials · doi:10.1038/s41563-020-0615-x · Cited by 236
Cancers make their own luck: theories of cancer origins
Jassim, A., Rahrmann, E. P., Simons, B. D., & Gilbertson, R. J. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00602-5 · Cited by 236
Life histories of myeloproliferative neoplasms inferred from phylogenies.
Williams, N., Lee, J., Mitchell, E., Moore, L., Baxter, E. J., Hewinson, J., Dawson, K. J., Menzies, A. H., Godfrey, A. L., Green, A. R., et al. (2022) · RePEc: Research Papers in Economics · doi:10.17863/cam.80309 · Cited by 216
Mammalian in vitro gametogenesis
Saitou, M., & Hayashi, K. (2021) · Science · doi:10.1126/science.aaz6830 · Cited by 218
An analysis of genetic heterogeneity in untreated cancers
Reiter, J. G., Baretti, M., Gerold, J. M., Makohon-Moore, A. P., DAUD, A. I., Iacobuzio–Donahue, C. A., Azad, N. S., Kinzler, K. W., Nowak, M. A., & Vogelstein, B. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0185-x · Cited by 213
Somatic Evolution in Non-neoplastic IBD-Affected Colon
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. (2020) · Cell · doi:10.1016/j.cell.2020.06.036 · Cited by 213
A mathematical model of ctDNA shedding predicts tumor detection size
Avanzini, S., Kurtz, D. M., Chabon, J. J., Moding, E. J., Hori, S. S., Gambhir, S. S., Alizadeh, A. A., Diehn, M., & Reiter, J. G. (2020) · Science Advances · doi:10.1126/sciadv.abc4308 · Cited by 217
Macroscopic somatic clonal expansion in morphologically normal human urothelium
Li, R., Du, Y., Chen, Z., Xu, D., Lin, T., Jin, S., Wang, G., Liu, Z., Lu, M., Chen, X., et al. (2020) · Science · doi:10.1126/science.aba7300 · Cited by 206
A body map of somatic mutagenesis in morphologically normal human tissues
Li, R., Di, L., Li, J., Fan, W., Liu, Y., Guo, W., Liu, W., Liu, L., Li, Q., Chen, L., et al. (2021) · Nature · doi:10.1038/s41586-021-03836-1 · Cited by 183
Moody, S., Senkin, S., Islam, S. M. A., Wang, J., Nasrollahzadeh, D., Penha, R. C. C., Fitzgerald, S. F., Bergstrom, E. N., Atkins, J., He, Y., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00928-6 · Cited by 192
Mutant clones in normal epithelium outcompete and eliminate emerging tumours
Colom, B., Herms, A., Hall, M. W. J., Dentro, S. C., King, C., Sood, R. K., Alcolea, M. P., Piedrafita, G., Fernandez-Antoran, D., Ong, S. H., et al. (2021) · Nature · doi:10.1038/s41586-021-03965-7 · Cited by 192
Montégut, L., López-Otín, C., & Kroemer, G. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02020-z · Cited by 222
“…all major organs, causing the generation of mosaics of cells (i.e., the juxtaposition of genetically non-identically cells within the same tissue), some of which tend to clonally expand because they acquire a proliferative advantage over normal, unmuted cells, hence outcompeting them [39, 40].”
BackgroundMolecular classification and diagnostics of upper urinary tract urothelial carcinoma
Fujii, Y. R., Sato, Y., Suzuki, H., Kakiuchi, N., Yoshizato, T., Lenis, A. T., Maekawa, S., Yokoyama, A., Takeuchi, Y., Inoue, Y., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.05.008 · Cited by 184
The landscape of gene mutations in cirrhosis and hepatocellular carcinoma
Müller, M., Bird, T. G., & Nault, J. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.01.019 · Cited by 182
The road ahead in genetics and genomics
McGuire, A. L., Gabriel, S., Tishkoff, S. A., Wonkam, A., Chakravarti, A., Furlong, E. E. M., Treutlein, B., Meissner, A., Chang, H. Y., López-Bigas, N., et al. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-0272-6 · Cited by 188
Somatic mutation and clonal expansions in human tissues
Martincorena, I. (2019) · Genome Medicine · doi:10.1186/s13073-019-0648-4 · Cited by 172
Transient loss of Polycomb components induces an epigenetic cancer fate
Parreno, V., Loubière, V., Schuettengruber, B., Fritsch, L., Rawal, C. C., Erokhin, M., Győrffy, B., Normanno, D., Stefano, M. D., Moreaux, J., et al. (2024) · Nature · doi:10.1038/s41586-024-07328-w · Cited by 180
Somatic Mutations in “Benign” Disease
Mustjoki, S. M., & Young, N. S. (2021) · New England Journal of Medicine · doi:10.1056/nejmra2101920 · Cited by 169
Spatial competition shapes the dynamic mutational landscape of normal esophageal epithelium
Colom, B., Alcolea, M. P., Piedrafita, G., Hall, M., Wabik, A., Dentro, S. C., Fowler, J. C., Herms, A., King, C., Ong, S. H., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0624-3 · Cited by 161
The critical roles of somatic mutations and environmental tumor-promoting agents in cancer risk
Balmain, A. (2020) · Nature Genetics · doi:10.1038/s41588-020-00727-5 · Cited by 152
Kumagai, S., Itahashi, K., & Nishikawa, H. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00870-6 · Cited by 171
“Cancer cells are known to evolve in the process of tumour initiation, progression and metastasis 218–220 .”
Cell competition in development, homeostasis and cancer
van Neerven, S. M., & Vermeulen, L. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00538-y · Cited by 163
Jakobsen, N. A., Turkalj, S., Zeng, A. G. X., Stoilova, B., Metzner, M., Rahmig, S., Nagree, M. S., Shah, S., Moore, R., Usukhbayar, B., et al. (2024) · Cell Stem Cell · doi:10.1016/j.stem.2024.05.010 · Cited by 130
Characterizing the ecological and evolutionary dynamics of cancer
Zahir, N., Sun, R., Gallahan, D., Gatenby, R. A., & Curtis, C. N. (2020) · Nature Genetics · doi:10.1038/s41588-020-0668-4 · Cited by 144
Clonal dynamics in early human embryogenesis inferred from somatic mutation
Park, S., Mali, N. M., Kim, R., Choi, J., Lee, J., Lim, J., Park, J. M., Park, J. W., Kim, D., Kim, T., et al. (2021) · Nature · doi:10.1038/s41586-021-03786-8 · Cited by 146
Impact of risk factors on early cancer evolution
Weeden, C. E., Hill, W., Lim, E. L., Gronroos, E. C., & Swanton, C. (2023) · Cell · doi:10.1016/j.cell.2023.03.013 · Cited by 147
Nam, A. S., Dusaj, N., Izzo, F., Murali, R., Myers, R. M., Mouhieddine, T. H., Sotelo, J., Benbarche, S., Waarts, M., Gaiti, F., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01179-9 · Cited by 140
Widman, A. J., Shah, M. J., Frydendahl, A., Halmos, D., Khamnei, C. C., Øgaard, N., Rajagopalan, S., Arora, A., Deshpande, A. S., Hooper, W. F., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03040-4 · Cited by 148
Cancer Stem Cells: From Historical Roots to a New Perspective
Capp, J. (2019) · Journal of Oncology · doi:10.1155/2019/5189232 · Cited by 137
“This would resolve many paradoxes concerning, for example, the widespread presence of so-called oncogenic alterations (that is to say, supposed to cause cancer) in healthy tissues, such as in the skin [95] or in the oesophagus [96].”
BackgroundThe Role of TP53 in Adaptation and Evolution
Voskarides, K., & Giannopoulou, N. (2023) · Cells · doi:10.3390/cells12030512 · Cited by 145
“This excessive clonal expansion is implicated in cancer development, highlighting the importance of lifestyle factors in carcinogenesis [49].”
BackgroundResultThe somatic mutation landscape of the human body
García-Nieto, P. E., Morrison, A. J., & Fraser, H. B. (2019) · Genome biology · doi:10.1186/s13059-019-1919-5 · Cited by 133
On the Origin of ATP Synthesis in Cancer
Seyfried, T. N., Arismendi-Morillo, G., Mukherjee, P., & Chinopoulos, C. (2020) · iScience · doi:10.1016/j.isci.2020.101761 · Cited by 121
Esophageal Cancer: Overview, Risk Factors, and Reasons for the Rise
Lander, S., Lander, E. M., & Gibson, M. K. (2023) · Current Gastroenterology Reports · doi:10.1007/s11894-023-00899-0 · Cited by 126
“Normal ageing can augment this process but is induced by a series of risk factors, such as alcohol, tobacco use, and genetic predispositions, discussed below [3, 4].”
BackgroundNotch1 mutations drive clonal expansion in normal esophageal epithelium but impair tumor growth
Abby, E., Dentro, S. C., Hall, M. W. J., Fowler, J. C., Ong, S. H., Sood, R., Herms, A., Piedrafita, G., Abnizova, I., Siebel, C. W., et al. (2023) · Nature Genetics · doi:10.1038/s41588-022-01280-z · Cited by 121
Dreßler, L., Bortolomeazzi, M., Keddar, M. R., Mišetić, H., Sartini, G., Acha‐Sagredo, A., Montorsi, L., Wijewardhane, N., Repana, D., Nulsen, J., et al. (2022) · Genome biology · doi:10.1186/s13059-022-02607-z · Cited by 119
Molecular mechanisms in colitis-associated colorectal cancer
Zhou, R. W., Harpaz, N., Itzkowitz, S. H., & Parsons, R. E. (2023) · Oncogenesis · doi:10.1038/s41389-023-00492-0 · Cited by 123
The translational challenges of precision oncology
Pich, O., Bailey, C., Watkins, T. B. K., Zaccaria, S., Jamal‐Hanjani, M., & Swanton, C. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.04.002 · Cited by 116
Outcompeting p53-Mutant Cells in the Normal Esophagus by Redox Manipulation
Fernández‐Antorán, D., Piedrafita, G., Murai, K., Ong, S. H., Herms, A., Frezza, C., & Jones, P. H. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.06.011 · Cited by 111
“This process is exemplified by human esophageal epithelium (EE), in which mutations generated by cell-intrinsic processes colonize the majority of normal epithelium by middle age (Martincorena et al., 2018; Yokoyama et al., 2019).”
BackgroundClonal hematopoiesis, somatic mosaicism, and age-associated disease
Evans, M. A., & Walsh, K. X. (2022) · Physiological Reviews · doi:10.1152/physrev.00004.2022 · Cited by 112
Si, D., Ageeva, E. S., & Żukow, W. (2022) · Journal of Education Health and Sport · doi:10.12775/jehs.2022.12.08.074 · Cited by 105
Tumor-Naïve Multimodal Profiling of Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma
Burgener, J., Zou, J., Zhao, Z., Zheng, Y., Shen, S. Y., Huang, S. H., Keshavarzi, S., Xu, W., Liu, F., Liu, G., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0110 · Cited by 102
Huang, K. K., Ma, H., Chong, R. H. H., Uchihara, T., Lian, B. S. X., Zhu, F., Sheng, T., Srivastava, S., Tay, S. T., Sundar, R., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.10.004 · Cited by 110
Principles of the Molecular and Cellular Mechanisms of Aging
da Silva, P. F. L., & Schumacher, B. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.11.018 · Cited by 106
Bernstein, N., Chapman, M. S., Nyamondo, K., Chen, Z., Williams, N., Mitchell, E., Campbell, P. J., Cohen, R. L., & Nangalia, J. (2024) · Nature Genetics · doi:10.1038/s41588-024-01755-1 · Cited by 108
“In total, 150 nonsynonymous variants were identified in 16 of the 17 new fitness-inferred CH drivers across these individuals (Supplementary Tables 7 and 9).”
Antagonistic Pleiotropy in Human Disease
Byars, S., & Voskarides, K. (2019) · Journal of Molecular Evolution · doi:10.1007/s00239-019-09923-2 · Cited by 96
Clonal hematopoiesis and associated diseases: A review of recent findings
Asada, S., & Kitamura, T. (2021) · Cancer Science · doi:10.1111/cas.15094 · Cited by 104
Organ System Crosstalk in Cardiometabolic Disease in the Age of Multimorbidity
Oishi, Y., & Manabe, I. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00064 · Cited by 98
“Similar age-related expansion of clones with driver mutations is observed in other normal tissues, including esophageal epithelium (109).”
BackgroundThe Origin and Immune Recognition of Tumor-Specific Antigens
Apavaloaei, A., Hardy, M., Thibault, P., & Perreault, C. (2020) · Cancers · doi:10.3390/cancers12092607 · Cited by 95
Age influences on the molecular presentation of tumours
Li, C. H., Haider, S. A., & Boutros, P. C. (2022) · Nature Communications · doi:10.1038/s41467-021-27889-y · Cited by 98
Mapping genomic and epigenomic evolution in cancer ecosystems
Ushijima, T., Clark, S. J., & Tan, P. B. O. (2021) · Science · doi:10.1126/science.abh1645 · Cited by 89
Dynamic Cancer Cell Heterogeneity: Diagnostic and Therapeutic Implications
Jacquemin, V., Antoine, M., Dom, G., Detours, V., Maenhaut, C., & Dumont, J. E. (2022) · Cancers · doi:10.3390/cancers14020280 · Cited by 92
“Genetic heterogeneity may also predate the tumor itself, as shown by the widespread prevalence—increasing with age—of oncogenic clones in non-tumoral esophagus [27,28].”
BackgroundTranslating insights into tumor evolution to clinical practice: promises and challenges
Fittall, M. W., & Loo, P. V. (2019) · Genome Medicine · doi:10.1186/s13073-019-0632-z · Cited by 91
Evolutionary histories of breast cancer and related clones
Nishimura, T., Kakiuchi, N., Yoshida, K., Sakurai, T., Kataoka, T. R., Kondoh, E., Chigusa, Y., Kawai, M., Sawada, M., Inoue, T., et al. (2023) · Nature · doi:10.1038/s41586-023-06333-9 · Cited by 85
Unveiling the link between chronic inflammation and cancer
Tripathi, S., Sharma, Y., & Kumar, D. (2025) · Metabolism Open · doi:10.1016/j.metop.2025.100347 · Cited by 103
“Surprisingly, comprehensive genomic research found that changes in cancer driver genes promote the age-related growth of cell clones in physiologically normal esophageal epithelia [27].”
Franco, I., Helgadottir, H. T., Moggio, A., Larsson, M., Vrtačnik, P., Johansson, A., Norgren, N., Lundin, P., Mas-Ponte, D., Nordström, J., et al. (2019) · Genome biology · doi:10.1186/s13059-019-1892-z · Cited by 83
“5b) and did not display the typical kidney cancer genetic lesions, nor mutations in TP53, a tumor suppressor often mutated in pre-cancer clones in human tissues [7, 8, 10] (Additional file 1: Table S5).”
BackgroundGenomic alterations driving precancerous to cancerous lesions in esophageal cancer development
Chang, J., Zhao, X., Wang, Y., Liu, T., Zhong, C., Lao, Y., Zhang, S., Liao, H., Bai, F., Lin, D., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.11.003 · Cited by 85
The duality of human oncoproteins: drivers of cancer and congenital disorders
Castel, P., Rauen, K. A., & McCormick, F. P. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0256-z · Cited by 80
Clonal dynamics of haematopoiesis across the human lifespanPreprint
Mitchell, E., Chapman, M. S., Williams, N., Dawson, K. J., Mende, N., Calderbank, E. F., Jung, H., Mitchell, T. J., Coorens, T. H. H., Spencer, D. H., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.16.456475 · Cited by 74
Epithelial defense against cancer (EDAC)
Tanimura, N., & Fujita, Y. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.05.011 · Cited by 71
Splicing Factor SRSF1 Promotes Pancreatitis and KRASG12D-Mediated Pancreatic Cancer
Wan, L., Lin, K., Rahman, M. A., Ishigami, Y., Wang, Z., Jensen, M. A., Wilkinson, J. E., Park, Y., Tuveson, D. A., & Krainer, A. R. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-1013 · Cited by 72
Metadata
- Authors
- Yokoyama, A., Kakiuchi, N., Yoshizato, T., Nannya, Y., Suzuki, H., Takeuchi, Y., Shiozawa, Y., Sato, Y., Aoki, K., Kim, S. K., Fujii, Y., Yoshida, K., Kataoka, K., Nakagawa, M. M., Inoue, Y., Hirano, T., Shiraishi, Y., Chiba, K., Tanaka, H., Sanada, M., Nishikawa, Y., Amanuma, Y., Ohashi, S., Aoyama, I., Horimatsu, T., Miyamoto, S., Tsunoda, S., Sakai, Y., Narahara, M., Brown, J. B., Sato, Y., Sawada, G., Mimori, K., Minamiguchi, S., Haga, H., Seno, H., Miyano, S., Makishima, H., Muto, M., & Ogawa, S.
- Affiliations
- Kyoto University (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Nagoya Medical Center (JP)
- Kyoto University Hospital (JP)
- McGill University (CA)
- Kyushu University Beppu Hospital (JP)
- Corresponding author
- Ogawa, Seishi
- ORCID
- Yokoyama, Akira
- Kakiuchi, Nobuyuki
- Yoshizato, Tetsuichi
- Nannya, Yasuhito
- Suzuki, Hiromichi
- Takeuchi, Yasuhide
- Shiozawa, Yusuke
- Sato, Yusuke
- Aoki, Kosuke
- Kim, Soo Ki
- Fujii, Yoichi
- Yoshida, Kenichi
- Kataoka, Keisuke
- Nakagawa, Masahiro M.
- Inoue, Yoshikage
- Hirano, Tomonori
- Shiraishi, Yuichi
- Chiba, Kenichi
- Tanaka, Hiroko
- Sanada, Masashi
- Nishikawa, Yoshitaka
- Ohashi, Shinya
- Horimatsu, Takahiro
- Miyamoto, Shin’ichi
- Tsunoda, Shigeru
- Sakai, Yoshiharu
- Sato, Yoshitaka
- Mimori, Koshi
- Minamiguchi, Sachiko
- Haga, Hironori
- Seno, Hiroshi
- Miyano, Satoru
- Makishima, Hideki
- Muto, Manabu
- Ogawa, Seishi
- Venue
- Nature
- Published
- 2019-01-02
- Volume
- 565
- Issue
- 7739
- Pages
- 312-317
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2905667684
- Cited by
- 628
- References
- 42
- Citations by year
- 2026: 43 · 2025: 54 · 2024: 64 · 2023: 97 · 2022: 109 · 2021: 95 · 2020: 106 · 2019: 58
- FWCI
- 19.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Funders
- Ministry of Education, Science and Technology
- Japan Society for the Promotion of Science (18H02692, 15H05791, 15H05912, 17K19595, 15H05909)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- esophageal epithelium, clonal expansion, driver mutations, Notch1, PPM1D, aging, esophageal squamous cell carcinoma, alcohol consumption, smoking, cancer risk, single-cell sequencing
- MeSH terms
- Mutation Accumulation, Protein Phosphatase 2C, Adolescent, Adult, Aged, Aged, 80 and over, Aging, Alcohol Drinking, Biopsy, Cell Count, Cell Transformation, Neoplastic, Child, Child, Preschool, Clone Cells, Epithelium, Esophageal Neoplasms, Female, Humans, Infant, Life Style, Male, Middle Aged, Mutation, Precancerous Conditions, Risk Factors, Smoking, Genome, Human, Sequence Analysis, DNA, Evolution, Molecular, Receptor, Notch1, Young Adult, DNA Copy Number Variations, Single-Cell Analysis, Gene-Environment Interaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
