Telomere-Driven Tetraploidization Occurs in Human Cells Undergoing Crisis and Promotes Transformation of Mouse Cells
Open accessAbstract
Human cancers with a subtetraploid karyotype are thought to originate from tetraploid precursors, but the cause of tetraploidization is unknown. We previously documented endoreduplication in mouse cells with persistent telomere dysfunction or genome-wide DNA damage. We now report that endoreduplication and mitotic failure occur during telomere crisis in human fibroblasts and mammary epithelial cells and document the role of p53 and Rb in repressing tetraploidization. Using an inducible system to generate transient telomere damage, we show that telomere-driven tetraploidization enhances the tumorigenic transformation of mouse cells. Similar to human solid cancers, the resulting tumors evolved subtetraploid karyotypes. These data establish that telomere-driven tetraploidization is induced by critically short telomeres and has the potential to promote tumorigenesis in early cancerous lesions.
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Loss of telomere function at a few chromosome ends is sufficient to induce replicative arrest.
“Loss of telomere function at a few chromosome ends in a cell is sufficient to induce replicative arrest9,39,40 (FIG. 2b).”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [9]
Telomere crisis can induce tetraploidization.
“Finally, telomere crisis can induce tetraploidization (doubling the set of chromosomes)8,9, which is inferred to be a frequent event during the development of human cancers125.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [9]
The repertoire of genomic alterations attributable to telomere crisis is more extensive and includes whole-genome reduplication, chromothripsis, and kataegis.
“However, it has recently become clear that the repertoire of genomic alterations that can be ascribed to telomere crisis is more extensive and includes whole-genome reduplication, chromothripsis and kataegis3,8,9.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [9]
Tetraploidization can be induced in cells lacking p53 and RB pathways that have a high load of dysfunctional telomeres.
“Tetraploidization can be induced in cells that lack the p53 and RB pathways, which have a high load of dysfunctional telomeres8,9 (FIG. 6).”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [9]
Tetraploidization triggered by permanently damaged telomeres promotes tumorigenic transformation of mouse cells.
“Subsequent work by the same team has shown that tetraploidization triggered by permanently damaged telomeres promotes tumorigenic transformation of mouse cells. 92”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [92]
In old cells lacking p53 and pRb, severe telomere shortening causes crisis, widespread death, and tetraploidization via endoreplication or failed mitosis.
“Similarly, in aging p53/pRbdeficient cells, extensive telomere erosion induces crisis with massive cell death and tetraploidization through endoreplication or mitotic failure.92”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [92]
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Cites
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L. C., Coviello, G. M., Wright, W. E., Weinrich, S. L., & Shay, J. W. (1994) · Science · doi:10.1126/science.7605428 · Cited by 7,091 · cited 1× · see citing works
“Due to the absence of telomerase (Kim et al., 1994), telomeres shorten with cell”
A DNA damage checkpoint response in telomere-initiated senescence
Fagagna, F. D. D., Reaper, P. M., Clay-Farrace, L., Fiegler, H., Carr, P., von Zglinicki, T., Saretzki, G., Carter, N. P., & Jackson, S. P. (2003) · Nature · doi:10.1038/nature02118 · Cited by 2,855 · cited 2× · see citing works
“…telomeres exposes the singlestranded DNA and permanently activates the ATR kinase pathway whereas critically shortened telomeres may be expected to lose several (or all) shelterin proteins rather than POT1 alone and are known to activate both ATM and ATR signaling (d'Adda di Fagagna et al., 2003).”
A survey of telomerase activity in human cancer
Shay, J. W., & Bacchetti, S. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(97)00062-2 · Cited by 2,794 · see citing works
Massive genomic rearrangement acquired in a single catastrophic event during cancer development
Stephens, P. J., Greenman, C. D., Fu, B., Yang, F., Bignell, G. R., Mudie, L. J., Pleasance, E. D., Lau, K. W., Beare, D., Stebbings, L. A., et al. (2011) · Cell · doi:10.1016/j.cell.2010.11.055 · Cited by 2,414 · see citing works
Genomic instability — an evolving hallmark of cancer
Negrini, S., Gorgoulis, V. G., & Halazonetis, T. D. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2858 · Cited by 2,397 · see citing works
Visualizing Spatiotemporal Dynamics of Multicellular Cell-Cycle Progression
Sakaue-Sawano, A., Kurokawa, H., Morimura, T., Hanyu, A., Hama, H., Osawa, H., Kashiwagi, S., Fukami, K., Miyata, T., Miyoshi, H., et al. (2008) · Cell · doi:10.1016/j.cell.2007.12.033 · Cited by 2,123 · see citing works
Counter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05245.x · Cited by 2,096 · cited 1× · see citing works
“Eventually, the cells enter telomere crisis, a stage in which the rampant genome instability associated with lack of telomere function curbs cell proliferation and survival (Wright and Shay, 1992; Shay et al., 1993; Shay and Wright, 2005; Counter et al., 1992).”
Genetic instability in colorectal cancers
Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1997) · Nature · doi:10.1038/386623a0 · Cited by 1,995 · see citing works
The DNA Damage Response: Ten Years After
Harper, J. W., & Elledge, S. J. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.11.015 · Cited by 1,705 · see citing works
Telomere reduction in human colorectal carcinoma and with ageing
Hastie, N. D., Dempster, M., Dunlop, M. G., Thompson, A. M., Green, D. K., & Allshire, R. C. (1990) · Nature · doi:10.1038/346866a0 · Cited by 1,650 · see citing works
Herbig, U., Jobling, W. A., Chen, B. P. C., Chen, D. J., & Sedivy, J. M. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00256-4 · Cited by 1,344 · cited 2× · see citing works
“After extensive proliferation, dysfunctional short telomeres are recognized as sites of DNA damage by the ATM and ATR kinases and induce p53/Rb-mediated senescence or apoptosis (d’Adda di Fagagna et al., 2003; Herbig et al., 2004).”
Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice
Artandi, S. E., Chang, S., Lee, S.-L., Alson, S., Gottlieb, G. J., Chin, L., & DePinho, R. A. (2000) · Nature · doi:10.1038/35020592 · Cited by 1,085 · see citing works
Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells
Fujiwara, T., Bandi, M., Nitta, M., Ivanova, E. V., Bronson, R. T., & Pellman, D. (2005) · Nature · doi:10.1038/nature04217 · Cited by 1,067 · see citing works
Baker, S. J., Preisinger, A. C., Jessup, J. M., Paraskeva, C., Markowitz, S. D., Willson, J. K. V., Hamilton, S. R., & Vogelstein, B. (1990) · PubMed · Cited by 1,065 · see citing works
Structure and variability of human chromosome ends.
de Lange, T., Shiue, L., Myers, R. M., Cox, D. R., Naylor, S. L., Killery, A. M., & Varmus, H. E. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.2.518 · Cited by 848 · see citing works
Telomeres and telomerase in cancer
Artandi, S. E., & DePinho, R. A. (2010) · Carcinogenesis · doi:10.1093/carcin/bgp268 · Cited by 823 · see citing works
Senescence Induced by Altered Telomere State, Not Telomere Loss
Karlseder, J., Smogorzewska, A., & de Lange, T. (2002) · Science · doi:10.1126/science.1069523 · Cited by 796 · see citing works
A role for both RB and p53 in the regulation of human cellular senescence*1
SHAY, J. (1991) · Experimental Cell Research · doi:10.1016/0014-4827(91)90453-2 · Cited by 757 · see citing works
Senescence and immortalization: role of telomeres and telomerase
Shay, J. W., & Wright, W. E. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh296 · Cited by 729 · see citing works
Durkin, S. G., & Glover, T. W. (2007) · Annual Review of Genetics · doi:10.1146/annurev.genet.41.042007.165900 · Cited by 715 · see citing works
Tetraploidy, aneuploidy and cancer
Ganem, N. J., Storchova, Z., & Pellman, D. (2007) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2007.02.011 · Cited by 668 · see citing works
DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion
Celli, G. B., & de Lange, T. (2005) · Nature Cell Biology · doi:10.1038/ncb1275 · Cited by 623 · see citing works
Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes
Romanov, S. R., Kozakiewicz, B. K., Holst, C. R., Stampfer, M. R., Haupt, L. M., & Tlsty, T. D. (2001) · Nature · doi:10.1038/35054579 · Cited by 560 · see citing works
Different telomere damage signaling pathways in human and mouse cells
Smogorzewska, A., & de Lange, T. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf433 · Cited by 482 · cited 1× · see citing works
“…the data argue that this pathway is similar in human and mouse cells, despite the distinctions in their telomere damage response pathways (Smogorzewska and de Lange, 2002; Jacobs and de Lange, 2004), and demonstrate the relevance of telomere-driven tetraploidization in epithelial cells,…”
The Causes and Consequences of Polyploidy in Normal Development and Cancer
Davoli, T., & de Lange, T. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154234 · Cited by 432 · see citing works
Self-citationHockemeyer, D., Daniels, J.-P., Takai, H., & de Lange, T. (2006) · Cell · doi:10.1016/j.cell.2006.04.044 · Cited by 397 · see citing works
The two-stage mechanism controlling cellular senescence and immortalization
Wright, W. E., & Shay, J. W. (1992) · Experimental Gerontology · doi:10.1016/0531-5565(92)90069-c · Cited by 383 · see citing works
Telomere Shortening Is Nearly Universal in Pancreatic Intraepithelial Neoplasia
van Heek, N. T., Meeker, A. K., Kern, S. E., Yeo, C. J., Lillemoe, K. D., Cameron, J. L., Offerhaus, G. J. A., Hicks, J. L., Wilentz, R. E., Goggins, M. G., et al. (2002) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64432-x · Cited by 363 · see citing works
The consequences of tetraploidy and aneuploidy
Storchova, Z., & Kuffer, C. (2008) · Journal of Cell Science · doi:10.1242/jcs.039537 · Cited by 363 · see citing works
In situ analyses of genome instability in breast cancer
Chin, K., de Solorzano, C. O., Knowles, D., Jones, A., Chou, W., Rodriguez, E. G., Kuo, W.-L., Ljung, B.-M., Chew, K., Myambo, K., et al. (2004) · Nature Genetics · doi:10.1038/ng1409 · Cited by 361 · see citing works
Telomere Length Abnormalities Occur Early in the Initiation of Epithelial Carcinogenesis
Meeker, A. K., Hicks, J. L., Iacobuzio-Donahue, C. A., Montgomery, E. A., Westra, W. H., Chan, T. Y., Ronnett, B. M., & De Marzo, A. M. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-0984-03 · Cited by 306 · see citing works
Persistent Telomere Damage Induces Bypass of Mitosis and Tetraploidy
Davoli, T., Denchi, E. L., & de Lange, T. (2010) · Cell · doi:10.1016/j.cell.2010.01.031 · Cited by 298 · see citing works
Self-citationTelomere shortening is an early somatic DNA alteration in human prostate tumorigenesis.
Meeker, A. K., Hicks, J. L., Platz, E. A., March, G. E., Bennett, C., Delannoy, M. J., & Marzo, A. M. D. (2002) · PubMed · Cited by 271 · see citing works
Model for the genetic evolution of human solid tumors.
Shackney, S. E., Smith, C., Miller, B. W., Burholt, D. R., Murtha, K., Giles, H. R., Ketterer, D. M., & Pollice, A. A. (1989) · PubMed · Cited by 252 · see citing works
Eukaryotic DNA replication control: Lock and load, then fire
Remus, D., & Diffley, J. F. X. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.08.002 · Cited by 245 · see citing works
Significant Role for p16INK4a in p53-Independent Telomere-Directed Senescence
Jacobs, J. J. L., & de Lange, T. (2004) · Current Biology · doi:10.1016/j.cub.2004.12.025 · Cited by 237 · cited 4× · see citing works
“Cell Culture Procedure and Viral Gene Delivery BJ (ATCC#: CRL2522) and IMR90 (ATCC#: CCl186) human fibroblasts were transduced with retroviral vectors expressing SV40-LT, HPV-E6/E7, or p53175H (p53 dn) as described in (Karlseder et al., 2002; Jacobs and de Lange, 2004).”
InfluentialG1 tetraploidy checkpoint and the suppression of tumorigenesis
Margolis, R. L., Lohez, O. D., & Andreassen, P. R. (2002) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10411 · Cited by 231 · see citing works
Arias, E. E., & Walter, J. C. (2004) · Genes & Development · doi:10.1101/gad.1255805 · Cited by 196 · see citing works
Telomere-related Genome Instability in Cancer
DE LANGE, T. (2005) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2005.70.032 · Cited by 182 · see citing works
Lin, T. T., Letsolo, B. T., Jones, R. E., Rowson, J., Pratt, G., Hewamana, S., Fegan, C., Pepper, C., & Baird, D. M. (2010) · Blood · doi:10.1182/blood-2010-02-272104 · Cited by 178 · see citing works
Shay, J. W., van der Haegen, B. A., Ying, Y., & Wright, W. E. (1993) · Experimental Cell Research · doi:10.1006/excr.1993.1283 · Cited by 164 · see citing works
Telomere Protection by TPP1 Is Mediated by POT1a and POT1b
Kibe, T., Osawa, G. A., Keegan, C. E., & de Lange, T. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01498-09 · Cited by 121 · see citing works
Response of men with advanced prostatic carcinoma to exogenous administration of testosterone
Prout, G. R., & Brewer, W. R. (1967) · Cancer · doi:10.1002/1097-0142(196711)20:11 · Cited by 111 · see citing works
Barrettʼs esophagus: ordering the events that lead to cancer
Reid, B. J., Barrett, M. T., Galipeau, P. C., Sanchez, C. A., Neshat, K., Cowan, D., & Levine, D. S. (1996) · European Journal of Cancer Prevention · doi:10.1097/00008469-199612002-00009 · Cited by 108 · see citing works
Meeker, A. K., & Argani, P. (2004) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1023/b:jomg.0000048775.04140.92 · Cited by 100 · see citing works
Molecular Evolutionary Patterns in Breast Cancer
Shackney, S. E., & Silverman, J. F. (2003) · Advances in Anatomic Pathology · doi:10.1097/00125480-200309000-00003 · Cited by 74 · see citing works
Garbe, J. C., Holst, C. R., Bassett, E., Tlsty, T. D., & Stampfer, M. R. (2007) · Cell Cycle · doi:10.4161/cc.6.15.4519 · Cited by 65 · see citing works
Ottesen, G. L. (2003) · PubMed · Cited by 33 · see citing works
Flagged first, then by citations
2 of the 50 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Davoli, T., Uno, H., Wooten, E. C., & Elledge, S. J. (2017) · Science · doi:10.1126/science.aaf8399 · Cited by 1,325 · see citing works
Self-citationTelomeres in cancer: tumour suppression and genome instability
Maciejowski, J., & de Lange, T. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.171 · Cited by 745 · see citing works
Chromothripsis and Kataegis Induced by Telomere Crisis
Maciejowski, J., Li, Y., Bosco, N., Campbell, P. J., & de Lange, T. (2015) · Cell · doi:10.1016/j.cell.2015.11.054 · Cited by 675 · see citing works
Context is everything: aneuploidy in cancer
Ben‐David, U., & Amon, A. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0171-x · Cited by 651 · see citing works
Medulloblastomics: the end of the beginning
Northcott, P. A., Jones, D., Kool, M., Robinson, G. W., Gilbertson, R. J., Cho, Y., Pomeroy, S. L., Korshunov, A., Lichter, P., Taylor, M. D., et al. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3410 · Cited by 661 · see citing works
Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma
Zheng, S., Cherniack, A. D., Dewal, N., Moffitt, R. A., Danilova, L., Murray, B. A., Lerario, A. M., Else, T., Knijnenburg, T. A., Ciriello, G., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.04.002 · Cited by 657 · see citing works
Genome doubling shapes the evolution and prognosis of advanced cancers
Bielski, C. M., Zehir, A., Penson, A. V., Donoghue, M. T. A., Chatila, W. K., Armenia, J., Chang, M. T., Schram, A. M., Jonsson, P., Bandlamudi, C., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0165-1 · Cited by 632 · see citing works
Dewhurst, S. M., McGranahan, N., Burrell, R. A., Rowan, A., Gronroos, E. C., Endesfelder, D., Joshi, T., Mouradov, D., Gibbs, P., Ward, R. L., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0285 · Cited by 450 · see citing works
Determinants and clinical implications of chromosomal instability in cancer
Sansregret, L., Vanhaesebroeck, B., & Swanton, C. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.198 · Cited by 396 · see citing works
Cytokinesis Failure Triggers Hippo Tumor Suppressor Pathway Activation
Ganem, N. J., Cornils, H., Chiu, S.-Y., O’Rourke, K. P., Arnaud, J., Yimlamai, D., Théry, M., Camargo, F. D., & Pellman, D. S. (2014) · Cell · doi:10.1016/j.cell.2014.06.029 · Cited by 375 · see citing works
Endocycles: a recurrent evolutionary innovation for post-mitotic cell growth
Edgar, B. A., Zielke, N., & Gutiérrez, C. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3756 · Cited by 360 · see citing works
Paired exome analysis of Barrett's esophagus and adenocarcinoma
Stachler, M. D., Taylor-Weiner, A. N., Peng, S., McKenna, A., Agoston, A. T., Odze, R. D., Davison, J. M., Nason, K. S., Loda, M. F., Leshchiner, I., et al. (2015) · Nature Genetics · doi:10.1038/ng.3343 · Cited by 366 · see citing works
Causes and consequences of centrosome abnormalities in cancer
Godinho, S. A., & Pellman, D. S. (2014) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0467 · Cited by 340 · see citing works
Endoreplication and polyploidy: insights into development and disease
Fox, D. T., & Duronio, R. J. (2013) · Development · doi:10.1242/dev.080531 · Cited by 331 · see citing works
Senescence from G2 arrest, revisited
Gire, V., & Dulić, V. (2015) · Cell Cycle · doi:10.1080/15384101.2014.1000134 · Cited by 300 · see citing works
Fly-FUCCI: A Versatile Tool for Studying Cell Proliferation in Complex Tissues
Zielke, N., Korzelius, J., van Straaten, M., Bender, K., Schuhknecht, G. F. P., Dutta, D., Xiang, J., & Edgar, B. A. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.020 · Cited by 286 · see citing works
Whole-genome doubling confers unique genetic vulnerabilities on tumour cells
Quinton, R. J., DiDomizio, A., Vittoria, M. A., Kotýnková, K., Ticas, C. J., Patel, S., Koga, Y., Vakhshoorzadeh, J., Hermance, N. M., Kuroda, T. S., et al. (2021) · Nature · doi:10.1038/s41586-020-03133-3 · Cited by 270 · see citing works
The impact of mitotic errors on cell proliferation and tumorigenesisPreprint
Levine, M. S., & Holland, A. J. (2018) · Genes & Development · doi:10.1101/gad.314351.118 · Cited by 268 · see citing works
The Role of Aneuploidy in Cancer EvolutionPreprint
Sansregret, L., & Swanton, C. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a028373 · Cited by 264 · see citing works
Niu, N., Mercado‐Uribe, I., & Liu, J. (2017) · Oncogene · doi:10.1038/onc.2017.72 · Cited by 266 · see citing works
Telomere-driven diseases and telomere-targeting therapies
Martínez, P., & Blasco, M. A. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201610111 · Cited by 257 · see citing works
The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis
Potapova, T., & Gorbsky, G. J. (2017) · Biology · doi:10.3390/biology6010012 · Cited by 218 · see citing works
The expanding implications of polyploidy
Schoenfelder, K. P., & Fox, D. T. (2015) · The Journal of Cell Biology · doi:10.1083/jcb.201502016 · Cited by 210 · see citing works
Linking abnormal mitosis to the acquisition of DNA damage
Ganem, N. J., & Pellman, D. S. (2012) · The Journal of Cell Biology · doi:10.1083/jcb.201210040 · Cited by 203 · see citing works
Complex interactions between the DNA-damage response and mammalian telomeres
Arnoult, N., & Karlseder, J. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3092 · Cited by 202 · see citing works
Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis
Nassour, J., Aguiar, L. G., Correia, A., Schmidt, T. T., Mainz, L., Przetocka, S., Haggblom, C., Tadepalle, N., Williams, A. E., Shokhirev, M. N., et al. (2023) · Nature · doi:10.1038/s41586-023-05710-8 · Cited by 201 · see citing works
The two sides of chromosomal instability: drivers and brakes in cancer
Hosea, R., Hillary, S., Naqvi, S., Wu, S., & Kasim, V. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01767-7 · Cited by 205 · see citing works
Mitotic spindle multipolarity without centrosome amplification
Maiato, H., & Logarinho, E. (2014) · Nature Cell Biology · doi:10.1038/ncb2958 · Cited by 190 · see citing works
Size Does Matter: Why Polyploid Tumor Cells are Critical Drug Targets in the War on Cancer
Coward, J. I. G., & Harding, A. S. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00123 · Cited by 192 · see citing works
Polyploidization in Liver Tissue
Gentric, G., & Desdouets, C. (2014) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.06.035 · Cited by 192 · see citing works
Polyploidy in liver development, homeostasis and disease
Donne, R., Saroul-Aïnama, M., Cordier, P., Celton-Morizur, S., & Desdouets, C. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0284-x · Cited by 188 · see citing works
A Tetraploid Intermediate Precedes Aneuploid Formation in Yeasts Exposed to Fluconazole
Harrison, B. D., Hashemi, J., Bibi, M., Pulver, R., Bavli, D., Nahmias, Y., Wellington, M., Sapiro, G., & Berman, J. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001815 · Cited by 174 · see citing works
The Polyploid State Plays a Tumor-Suppressive Role in the Liver
Zhang, S., Zhou, K., Luo, X., Li, L., Tu, H.-C., Sehgal, A., Nguyen, L. H., Zhang, Y., Gopal, P., Tarlow, B. D., et al. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.01.010 · Cited by 180 · see citing works
DNA damage associated with mitosis and cytokinesis failure
Hayashi, M., & Karlseder, J. (2013) · Oncogene · doi:10.1038/onc.2012.615 · Cited by 165 · see citing works
Mammalian DNA2 helicase/nuclease cleaves G‐quadruplex DNA and is required for telomere integrity
Lin, W., Sampathi, S., Dai, H., Liu, C., Zhou, M., Hu, J., Huang, Q. M., Campbell, J. L., Shin‐ya, K., Zheng, L., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.88 · Cited by 166 · see citing works
Linking genomic reorganization to tumor initiation via the giant cell cycle
Niu, N., Zhang, J., Zhang, N., Mercado‐Uribe, I., Tao, F.-Y., Han, Z., Pathak, S., Multani, A. S., Kuang, J., Yao, J., et al. (2016) · Oncogenesis · doi:10.1038/oncsis.2016.75 · Cited by 170 · see citing works
Polyploid Giant Cancer Cells (PGCCs): The Evil Roots of Cancer
Chen, J., Niu, N., Zhang, J., Qi, L., Shen, W., Donkena, K. V., Feng, Z., & Liu, J. (2019) · Current Cancer Drug Targets · doi:10.2174/1568009618666180703154233 · Cited by 165 · see citing works
Deng, Z., Glousker, G., Molczan, A., Fox, A. J., Lamm, N., Dheekollu, J., Weizman, O.-E., Schertzer, M. J., Wang, Z., Vladimirova, O. V., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300600110 · Cited by 161 · see citing works
Therapeutic Targeting of Telomerase
Jäger, K., & Walter, M. (2016) · Genes · doi:10.3390/genes7070039 · Cited by 142 · see citing works
van Agtmaal, E. L., André, L. M., Willemse, M. P., Cumming, S. A., van Kessel, I. D. G., van den Broek, W. J. A. A., Gourdon, G., Furling, D., Mouly, V., Monckton, D. G., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2016.10.014 · Cited by 137 · see citing works
Undifferentiated Sarcomas Develop through Distinct Evolutionary Pathways
Steele, C. D., Tarabichi, M., Oukrif, D., Webster, A. P., Ye, H., Fittall, M. W., Lombard, P., Martincorena, I., Tarpey, P. S., Collord, G., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.02.002 · Cited by 132 · see citing works
Roles and mechanisms of cellular senescence in regulation of tissue homeostasis
Ohtani, N., & Hara, E. (2013) · Cancer Science · doi:10.1111/cas.12118 · Cited by 120 · see citing works
The “life code”: A theory that unifies the human life cycle and the origin of human tumors
Liu, J. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.09.005 · Cited by 119 · see citing works
Hickman, M. A., Paulson, C., Dudley, A., & Berman, J. (2015) · Genetics · doi:10.1534/genetics.115.178020 · Cited by 113 · see citing works
A three-state model of telomere control over human proliferative boundaries
Cesare, A. J., & Karlseder, J. (2012) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.08.007 · Cited by 106 · see citing works
A second chance for telomerase reverse transcriptase in anticancer immunotherapy
Zanetti, M. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.67 · Cited by 102 · see citing works
Polyploidy spectrum: a new marker in HCC classification
Bou-Nader, M., Caruso, S., Donné, R., Celton-Morizur, S., Calderaro, J., Gentric, G., Cadoux, M., L’Hermitte, A., Klein, C., Guilbert, T., et al. (2019) · Gut · doi:10.1136/gutjnl-2018-318021 · Cited by 91 · see citing works
Genome chaos: Creating new genomic information essential for cancer macroevolution
Heng, J., & Heng, H. H. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.11.003 · Cited by 101 · see citing works
Eichenlaub, T., Cohen, S. M., & Herranz, H. (2016) · Current Biology · doi:10.1016/j.cub.2015.12.042 · Cited by 97 · see citing works
Acquired resistance to combined BET and CDK4/6 inhibition in triple-negative breast cancer
Ge, J. Y., Shu, S., Kwon, M., Jovanović, B., Murphy, K. C., Gulvady, A. C., Fassl, A., Trinh, A. C., Kuang, Y., Heavey, G. A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16170-3 · Cited by 98 · see citing works
Polyploidy formation in cancer cells: How a Trojan horse is born
Waś, H., Borkowska, A., Olszewska, A., Klemba, A., Marciniak, M., Synowiec, A., & Kiéda, C. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.03.003 · Cited by 98 · see citing works
Genetic instability: tipping the balance
Janssen, A., & Medema, R. H. (2012) · Oncogene · doi:10.1038/onc.2012.576 · Cited by 97 · see citing works
From “Cellular” RNA to “Smart” RNA: Multiple Roles of RNA in Genome Stability and Beyond
Michelini, F., Jalihal, A. P., Francia, S., Meers, C., Neeb, Z. T., Rossiello, F., Gioia, U., Aguado, J., Jones-Weinert, C., Luke, B., et al. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00487 · Cited by 85 · see citing works
Docetaxel-induced polyploidization may underlie chemoresistance and disease relapse
Ogden, A., Rida, P. C. G., Knudsen, B. S., Kucuk, O., & Aneja, R. (2015) · Cancer Letters · doi:10.1016/j.canlet.2015.06.025 · Cited by 84 · see citing works
Hassel, C. A., Zhang, B., Dixon, M. J., & Calvi, B. R. (2013) · Development · doi:10.1242/dev.098871 · Cited by 78 · see citing works
Role of Telomeres and Telomeric Proteins in Human Malignancies and Their Therapeutic Potential
Fernandes, S. G., Dsouza, R., Pandya, G., Kirtonia, A., Tergaonkar, V., Lee, S. Y., Garg, M., & Khattar, E. (2020) · Cancers · doi:10.3390/cancers12071901 · Cited by 79 · see citing works
Centrosome dysfunction: a link between senescence and tumor immunity
Wu, Q., Li, B., Liu, L., Sun, S., & Sun, S. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00214-7 · Cited by 76 · see citing works
Cellular Plasticity: A Route to Senescence Exit and Tumorigenesis
Blander, H. D., Morel, A., Senaratne, A. P., Ouzounova, M., & Puisieux, A. (2021) · Cancers · doi:10.3390/cancers13184561 · Cited by 74 · see citing works
Indispensable pre-mitotic endocycles promote aneuploidy in the Drosophila rectum
Schoenfelder, K. P., Montague, R. A., Paramore, S. V., Lennox, A. L., Mahowald, A. P., & Fox, D. T. (2014) · Development · doi:10.1242/dev.109850 · Cited by 73 · see citing works
Potapova, T., Seidel, C. W., Box, A., Rancati, G. I., & Li, R. (2016) · Molecular Biology of the Cell · doi:10.1091/mbc.e16-05-0268 · Cited by 67 · see citing works
Paradoxes of cancer: Survival at the brink
Erenpreisa, J. A., Salmiņa, K., Anatskaya, O. V., & Cragg, M. S. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.12.009 · Cited by 71 · see citing works
Targeting tumor cell senescence and polyploidy as potential therapeutic strategies
Saleh, T., Carpenter, V. J., Bloukh, S., & Gewirtz, D. A. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.12.010 · Cited by 70 · see citing works
Chromosomal instability-induced senescence potentiates cell non-autonomous tumourigenic effects
He, Q., Au, B. V., Kulkarni, M., Shen, Y., Lim, K. J., Maimaiti, J., Wong, C. K., Luijten, M., Chong, H. C., Lim, E. H., et al. (2018) · Oncogenesis · doi:10.1038/s41389-018-0072-4 · Cited by 74 · see citing works
Induced dicentric chromosome formation promotes genomic rearrangements and tumorigenesis
Gascoigne, K. E., & Cheeseman, I. M. (2013) · Chromosome Research · doi:10.1007/s10577-013-9368-6 · Cited by 65 · see citing works
Control of Cellular Aging, Tissue Function, and Cancer by p53 Downstream of TelomeresPreprint
Roake, C. M., & Artandi, S. E. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026088 · Cited by 67 · see citing works
“Mitotic Slippage” and Extranuclear DNA in Cancer Chemoresistance: A Focus on Telomeres
Salmiņa, K., Bojko, A., Inashkina, I., Staniak, K., Dudkowska, M., Podlesniy, P., Rūmnieks, F., Vainshelbaum, N. M., Pjanova, D., Sikora, E., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082779 · Cited by 65 · see citing works
Telomeres and Cancer: Resolving the Paradox
Nassour, J., Schmidt, T. T., & Karlseder, J. (2021) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-050420-023410 · Cited by 64 · see citing works
Boscolo‐Rizzo, P., Mosto, M. C. D., Rampazzo, E., Giunco, S., Mistro, A. D., Menegaldo, A., Baboçi, L., Mantovani, M., Tirelli, G., & Rossi, A. D. (2016) · Cancer and Metastasis Reviews · doi:10.1007/s10555-016-9633-1 · Cited by 62 · see citing works
Telomeres and Telomerase in the Development of Liver Cancer
der Stroth, L. I., Tharehalli, U., Güneş, Ç., & Lechel, A. (2020) · Cancers · doi:10.3390/cancers12082048 · Cited by 63 · see citing works
Aneuploidy and complex genomic rearrangements in cancer evolution
Baker, T. M., Waise, S., Tarabichi, M., & Loo, P. V. (2024) · Nature Cancer · doi:10.1038/s43018-023-00711-y · Cited by 59 · see citing works
Tetraploidy in cancer and its possible link to aging
Tanaka, K., Goto, H., Nishimura, Y., Kasahara, K., Mizoguchi, A., & Inagaki, M. (2018) · Cancer Science · doi:10.1111/cas.13717 · Cited by 54 · see citing works
Tanaka, H., Goto, H., Inoko, A., Makihara, H., Enomoto, A., Horimoto, K., Matsuyama, M., Kurita, K., Izawa, I., & Inagaki, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.633891 · Cited by 55 · see citing works
Herranz, H., Eichenlaub, T., & Cohen, S. M. (2016) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2015.11.037 · Cited by 49 · see citing works
Failure of cell cleavage induces senescence in tetraploid primary cells
Panopoulos, A., Pacios-Bras, C., Choi, J., Mythili, Y., Sussman, M. A., Fotedar, R., & Margolis, R. L. (2014) · Molecular Biology of the Cell · doi:10.1091/mbc.e14-03-0844 · Cited by 47 · see citing works
Proliferation of Double-Strand Break-Resistant Polyploid Cells Requires Drosophila FANCD2
Bretscher, H. S., & Fox, D. T. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.05.004 · Cited by 46 · see citing works
PICH and TOP3A cooperate to induce positive DNA supercoiling
Bizard, A. H., Allemand, J., Hassenkam, T., Paramasivam, M., Sarlós, K., Singh, M. I., & Hickson, I. D. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0201-6 · Cited by 45 · see citing works
Asymmetric clustering of centrosomes defines the early evolution of tetraploid cells
Baudoin, N., Nicholson, J. M., Soto, K., Martin, O., Chen, J., & Cimini, D. (2019) · bioRxiv · doi:10.7554/elife.54565 · Cited by 38 · see citing works
Whole-genome doubling in tissues and tumors
Vittoria, M. A., Quinton, R. J., & Ganem, N. J. (2023) · Trends in Genetics · doi:10.1016/j.tig.2023.08.004 · Cited by 43 · see citing works
́Alcontres, M. S. D., Palacios, A., Mejias, D., & Blasco, M. A. (2014) · Cell Cycle · doi:10.4161/cc.28419 · Cited by 40 · see citing works
Hyperdiploid tumor cells increase phenotypic heterogeneity within Glioblastoma tumors.
Donovan, P., Cato, K., Legaie, R. A., Jayalath, R., Olsson, G., Hall, B., Olson, S., Boros, S., Reynolds, B., & Harding, A. (2014) · Molecular Biosystems · doi:10.1039/c3mb70484j · Cited by 34 · see citing works
Lynch, A. M., Eastmond, D. A., Elhajouji, A., Frötschl, R., Kirsch‐Volders, M., Marchetti, F., Masumura, K., Pacchierotti, F., Schuler, M., & Tweats, D. J. (2019) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2019.02.006 · Cited by 43 · see citing works
Whole-genome duplication increases tumor cell sensitivity to MPS1 inhibition
Jèmaà, M., Manic, G., Lledo, G., Lissa, D., Reynès, C., Morin, N., Chibon, F., Sistigu, A., Castedo, M., Vitale, I., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.6432 · Cited by 40 · see citing works
Polyteny: still a giant player in chromosome research
Stormo, B. M., & Fox, D. T. (2017) · Chromosome Research · doi:10.1007/s10577-017-9562-z · Cited by 40 · see citing works
Altamirano, S., Li, Z.-M., Fu, M., Ding, M., Fulton, S. R., Yoder, J., Tran, V., & Nielsen, K. (2021) · bioRxiv · doi:10.1128/mbio.02509-21 · Cited by 35 · see citing works
Lossaint, G., Horvat, A., Gire, V., Bačević, K., Mrouj, K., Charrier‐Savournin, F., Georget, V., Fisher, D., & Dulić, V. (2022) · Journal of Cell Science · doi:10.1242/jcs.259114 · Cited by 40 · see citing works
The origins and functions of hepatic polyploidy
Zhang, S., Lin, Y.-H., Tarlow, B., & Zhu, H. (2019) · Cell Cycle · doi:10.1080/15384101.2019.1618123 · Cited by 38 · see citing works
Telomeres as hotspots for innate immunity and inflammation
Nassour, J., Przetocka, S., & Karlseder, J. (2023) · DNA repair · doi:10.1016/j.dnarep.2023.103591 · Cited by 40 · see citing works
Karyotypic Aberrations in Oncogenesis and Cancer Therapy
Vitale, I., Manic, G., Senovilla, L., Kroemer, G., & Galluzzi, L. (2015) · Trends in Cancer · doi:10.1016/j.trecan.2015.08.001 · Cited by 34 · see citing works
Shoshani, O., Massalha, H., Shani, N., Kagan, S., Ravid, O., Madar, S., Trakhtenbrot, L., Leshkowitz, D., Rechavi, G., & Zipori, D. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1155 · Cited by 35 · see citing works
Cell populations can use aneuploidy to survive telomerase insufficiency
Millet, C., Ausiannikava, D., Bihan, T. L., Granneman, S., & Makovets, S. (2015) · Nature Communications · doi:10.1038/ncomms9664 · Cited by 36 · see citing works
Segeren, H. A., van Rijnberk, L. M., Moreno, E., Riemers, F. M., van Liere, E. A., Yuan, R., Wubbolts, R., de Bruin, A., & Westendorp, B. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108449 · Cited by 36 · see citing works
Zhao, N., Yin, G., Liu, C., Zhang, W., Shen, Y., Wang, D., Lin, Z., Yang, J., Mao, J., Guo, R., et al. (2023) · Cell Discovery · doi:10.1038/s41421-023-00538-y · Cited by 34 · see citing works
Loss of Telomere Protection: Consequences and Opportunities
Jacobs, J. J. L. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00088 · Cited by 37 · see citing works
Whole chromosome loss and associated breakage–fusion–bridge cycles transform mouse tetraploid cells
Thomas, R., Marks, D. H., Chin, Y., & Benezra, R. (2017) · The EMBO Journal · doi:10.15252/embj.201797630 · Cited by 35 · see citing works
Transient endoreplication down-regulates the kinesin-14 HSET and contributes to genomic instability
Chen, S., Stout, J. R., Dharmaiah, S., Yde, S. E., Calvi, B., & Walczak, C. (2016) · Molecular Biology of the Cell · doi:10.1091/mbc.e16-03-0159 · Cited by 30 · see citing works
Understanding telomere diseases through analysis of patient-derived iPS cells
Batista, L. F. Z., & Artandi, S. E. (2013) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.07.006 · Cited by 33 · see citing works
The genomics of undifferentiated sarcoma of soft tissue: Progress, challenges and opportunities
Steele, C. D., & Pillay, N. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.11.009 · Cited by 33 · see citing works
Genomic instability: Crossing pathways at the origin of structural and numerical chromosome changes
Russo, A., Pacchierotti, F., Cimini, D., Ganem, N. J., Genescà, A., Natarajan, A. T., Pavanello, S., Valle, G., & Degrassi, F. (2015) · Environmental and Molecular Mutagenesis · doi:10.1002/em.21945 · Cited by 32 · see citing works
Crane, M. M., Russell, A. E., Schafer, B. J., Blue, B. W., Whalen, R. M., Almazan, J. D., Hong, M. G., Nguyen, B., Goings, J. E., Chen, K. L., et al. (2019) · eLife · doi:10.7554/elife.50778 · Cited by 32 · see citing works
Bao, C., Tourdot, R. W., Brunette, G. J., Stewart, C., Sun, L., Baba, H., Watanabe, M., Agoston, A. T., Jajoo, K., Davison, J. M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41805-6 · Cited by 37 · see citing works
- Authors
- Davoli, T., & de Lange, T.
- Affiliations
- Rockefeller University (US)
- ORCID
- Davoli, Teresa
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 21
- Issue
- 6
- Pages
- 765-776
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3376354
- OpenAlex
- W2121212012
- Cited by
- 242
- References
- 50
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 12 · 2023: 17 · 2022: 8 · 2021: 27 · 2020: 20 · 2019: 16 · 2018: 28 · 2017: 17 · 2016: 19 · 2015: 18 · 2014: 17 · 2013: 14 · 2012: 12
- FWCI
- 13.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 447 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Cancer Society
- Breast Cancer Research Foundation
- National Institutes of Health (CA160924)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- tetraploidization, telomere crisis, endoreduplication, mitotic failure, p53, Rb, telomere dysfunction, carcinogenesis, fibroblasts, mammary epithelial cells
- MeSH terms
- Animals, Cell Line, Cell Transformation, Neoplastic, Cells, Cultured, DNA Damage, Epithelial Cells, Fibroblasts, Flow Cytometry, Humans, Mitosis, Time Factors, Immunoblotting, Tumor Suppressor Protein p53, Retinoblastoma Protein, Telomere, In Situ Hybridization, Fluorescence, RNA Interference, Mammary Glands, Human, Mice, Tetraploidy, Cell Cycle Checkpoints, Karyotype
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