Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice
Abstract
Aged humans sustain a high rate of epithelial cancers such as carcinomas of the breast and colon, whereas mice carrying common tumour suppressor gene mutations typically develop soft tissue sarcomas and lymphomas. Among the many factors that may contribute to this species variance are differences in telomere length and regulation. Telomeres comprise the nucleoprotein complexes that cap the ends of eukaryotic chromosomes and are maintained by the reverse transcriptase, telomerase. In human cells, insufficient levels of telomerase lead to telomere attrition with cell division in culture and possibly with ageing and tumorigenesis in vivo. In contrast, critical reduction in telomere length is not observed in the mouse owing to promiscuous telomerase expression and long telomeres. Here we provide evidence that telomere attrition in ageing telomerase-deficient p53 mutant mice promotes the development of epithelial cancers by a process of fusion-bridge breakage that leads to the formation of complex non-reciprocal translocations--a classical cytogenetic feature of human carcinomas. Our data suggest a model in which telomere dysfunction brought about by continual epithelial renewal during life generates the massive ploidy changes associated with the development of epithelial cancers.
Integrity signals
Registry
Cites
Statistics
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?
p53 deficiency in mTerc-/- mice results in near-complete rescue of adverse cellular consequences associated with telomere dysfunction, including cellular growth arrest and apoptosis, progressive organ system atrophy, and physiological compromise.
“Specifically, p53 deficiency results in nearcomplete rescue of adverse cellular consequences associated with telomere dysfunction, including cellular growth arrest and apoptosis, progressive organ system atrophy, and physiological compromise.”
From <i>Ink4a</i> / <i>Arf</i> tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse (2007) · cites this paper as [5]
mTerc-/- p53 mutant mice experience a dramatic increase in cancer incidence, a shift in tumor spectrum toward epithelial cancers, and accumulation of marked chromosomal aberrations targeting cancer-relevant loci.
“Although enabling cellular growth and survival and masking degenerative phenotypes, these mTerc -/ -p53 mutant mice experience a dramatic increase in cancer incidence, shift in tumor spectrum toward epithelial cancers, and accumulation of marked chromosomal aberrations targeting cancerrelevant loci for amplification and deletion (4-6).”
From <i>Ink4a</i> / <i>Arf</i> tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse (2007) · cites this paper as [5]
Telomere dysfunction has been shown to dramatically affect the tumor spectrum of late-generation mTerc-/- p53 mutant mice.
“Telomere dysfunction has been shown to dramatically affect the tumor spectrum of late-generation mTerc -/ -p53 mutant mice (5).”
From <i>Ink4a</i> / <i>Arf</i> tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse (2007) · cites this paper as [5]
When the p53 checkpoint is compromised, unchecked genomic instability caused by telomere dysfunction accelerates tumorigenesis as seen in late-generation mTerc-/- p53 mutant mice.
“When the p53 checkpoint is compromised, unchecked genomic instability caused by telomere dysfunction accelerates tumorigenesis as seen in late-generation mTerc -/ -p53 mutant mice (4, 5).”
From <i>Ink4a</i> / <i>Arf</i> tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse (2007) · cites this paper as [5]
The ongoing genomic instability permitted by p53 deficiency allowed for emergence of tumors with more complex karyotypes, reflected in a shift in tumor spectrum, from lymphomas and sarcomas in a setting of intact telomeres toward epithelial cancers in mice with telomere dysfunction.
“The ongoing genomic instability permitted by p53 deficiency allowed for emergence of tumors with more complex karyotypes, reflected in a shift in tumor spectrum, from lymphomas and sarcomas in a setting of intact telomeres toward epithelial cancers in mice with telomere dysfunction (5).”
From <i>Ink4a</i> / <i>Arf</i> tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse (2007) · cites this paper as [5]
Genome instability in cells undergoing telomere crisis was initially found to cause aneuploidy, translocations, loss of heterozygosity, and regional amplification through breakage-fusion-bridge cycles.
“Genome instability in cells undergoing telomere crisis was initially found to give rise to chromosome gains and losses (aneuploidy), translocations, gene loss (manifested as loss of heterozygosity (LOH)) and regional amplification through breakage–fusion–bridge (BFB) cycles1,80,83.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [1]
Malignant progression requires a period similar to telomere crisis that can result in large-scale genome rearrangements commonly seen in tumors.
“These observations indicate that malignant progression requires a period similar to the telomere crisis that can result in large-scale genome rearrangements of the kind commonly seen in tumors [349,351].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [351]
p53-mutant mice are cancer prone but their predilection for mesenchymal and lymphoid malignancies rather than epithelial cancers does not match the tumor types most commonly possessing p53 mutations in humans.
“while p53-mutant mice are cancer prone, we noted that their predilection for mesenchymal and lymphoid malignancies, rather than epithelial cancers, did not represent the tumor types most commonly possessing p53 mutations in humans (101,102).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [102]
Late generation mTerc−/− p53+/− mice emerged with a tumor spectrum resembling aged humans: carcinomas of skin, breast, and intestine with cytogenetic hallmarks of telomere dysfunction.
“As a further demonstration of the impact of p53 status on dysfunctional telomere-induced tumor growth, late generation mTerc−/− p53+/− mice emerged with a tumor spectrum that strikingly resembled those of aged humans: carcinomas of the skin, breast, and intestine with cytogenetic hallmarks of telomere dysfunction emerged as the largest group of tumors47.”
From Telomere dysfunction and tumour suppression: the senescence connection (2008) · cites this paper as [47]
Cites
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750 · see citing works
Creation of human tumour cells with defined genetic elements
Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., & Weinberg, R. A. (1999) · Nature · doi:10.1038/22780 · Cited by 2,345 · see citing works
Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
Blasco, M. A., Lee, H.-W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997) · Cell · doi:10.1016/s0092-8674(01)80006-4 · Cited by 2,108 · see citing works
Self-citationTRF2 Protects Human Telomeres from End-to-End Fusions
van Steensel, B., Smogorzewska, A., & de Lange, T. (1998) · Cell · doi:10.1016/s0092-8674(00)80932-0 · Cited by 1,709 · see citing works
Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice
Rudolph, K. L., Chang, S., Lee, H.-W., Blasco, M., Gottlieb, G. J., Greider, C., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80580-2 · Cited by 1,349 · cited 1× · see citing works
“, telomere shortening in ageing mTERC -/- mice is associated with increased rates of cancer, suggesting that the genetic instability associated with telomere dysfunction can facilitate transformation in vivo”
BackgroundSelf-citationEssential role of mouse telomerase in highly proliferative organs
Lee, H.-W., Blasco, M. A., Gottlieb, G. J., Horner, J. W., Greider, C. W., & DePinho, R. A. (1998) · Nature · doi:10.1038/33345 · Cited by 1,270 · cited 1× · see citing works
“Mice lacking the RNA component of telomerase (mTERC) exhibit progressive telomere shortening and ultimately chromosomal instability (end-to-end fusions) as a function of age and of successive generational mating”
BackgroundSelf-citationChin, L., Artandi, S. E., Shen, Q., Tam, A., Lee, S.-L., Gottlieb, G. J., Greider, C. W., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80762-x · Cited by 979 · cited 1× · see citing works
“In the setting of p53 deficiency, telomere dysfunction confers a greater susceptibility to transformation by cellular oncogene”
BackgroundSelf-citationTelomerase activity in ductal carcinoma in situ of the breast
Shpitz, B., Zimlichman, S., Zemer, R., Bomstein, Y., Zehavi, T., Liverant, S., Bernehim, J., Kaufman, Z., Klein, E., Shapira, Y., et al. (1999) · Breast Cancer Research and Treatment · doi:10.1023/a:1006394209922 · Cited by 46 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Hingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609 · see citing works
Self-citationMassive 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
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708 · see citing works
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486 · see citing works
Aubert, G., & Lansdorp, P. M. (2008) · Physiological Reviews · doi:10.1152/physrev.00026.2007 · Cited by 1,188 · 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
The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita
Vulliamy, T., Marrone, A., Goldman, F., Dearlove, A., Bessler, M., Mason, P. J., & Dokal, I. (2001) · Nature · doi:10.1038/35096585 · Cited by 960 · see citing works
DePinho, R. A. (2000) · Nature · doi:10.1038/35041694 · Cited by 951 · 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
Linking functional decline of telomeres, mitochondria and stem cells during ageing
Sahin, E., & DePinho, R. A. (2010) · Nature · doi:10.1038/nature08982 · Cited by 759 · see citing works
Self-citationChromothripsis 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
Tumor suppression by Ink4a-Arf: progress and puzzles.
Lowe, S. W., & Sherr, C. J. (2003) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00013-8 · Cited by 699 · see citing works
Telomeres: history, health, and hallmarks of aging
Chakravarti, D., LaBella, K. A., & DePinho, R. A. (2021) · Cell · doi:10.1016/j.cell.2020.12.028 · Cited by 637 · see citing works
Self-citationLovejoy, C. A., Li, W., Reisenweber, S., Thongthip, S., Bruno, J., de Lange, T., De, S., Petrini, J. H. J., Sung, P. A., Jasin, M., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002772 · Cited by 629 · see citing works
“LXN, IIICF/c, and LFS-05F-24) showed frequent nonreciprocal translocations, deletions, complex rearrangements, and hyper-triploid chromosome numbers (Figure 3), all of which can be caused by telomere dysfunction [40,41].”
BackgroundNormal 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
Telomere dysfunction and evolution of intestinal carcinoma in mice and humans
Rudolph, K. L., Millard, M., Bosenberg, M. W., & DePinho, R. A. (2001) · Nature Genetics · doi:10.1038/88871 · Cited by 527 · see citing works
Self-citationHallmarks of senescence in carcinogenesis and cancer therapy
Shay, J. W., & Roninson, I. B. (2004) · Oncogene · doi:10.1038/sj.onc.1207518 · Cited by 502 · see citing works
Rodriguez-Martin, B., Alvarez, E. G., Baez-Ortega, A., Zamora, J., Supek, F., Demeulemeester, J., Santamarina, M., Ju, Y. S., Temes, J., Garcia-Souto, D., et al. (2020) · Nature Genetics · doi:10.1038/s41588-019-0562-0 · Cited by 451 · 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 · see citing works
Telomere length and risk of incident cancer and cancer mortality
Willeit, P., Willeit, J., Mayr, A., Weger, S., Oberhollenzer, F., Brandstätter, A., Kronenberg, F., & Kiechl, S. (2010) · JAMA · doi:10.1001/jama.2010.897 · Cited by 484 · see citing works
Choudhury, A. R., Ju, Z., Djojosubroto, M. W., Schienke, A., Lechel, A., Schaetzlein, S., Jiang, H., Stepczynska, A., Wang, C., Buer, J., et al. (2007) · Nature Genetics · doi:10.1038/ng1937 · Cited by 426 · see citing works
Wu, L., Multani, A. S., He, H., Cosme-Blanco, W., Deng, Y., Deng, J. M., Bachilo, O., Pathak, S., Tahara, H., Bailey, S. M., et al. (2006) · Cell · doi:10.1016/j.cell.2006.05.037 · Cited by 422 · see citing works
Self-citationDanazol Treatment for Telomere Diseases
Townsley, D. M., Dumitriu, B., Liu, D., Biancotto, A., Weinstein, B., Chen, C., Hardy, N., Mihalek, A. D., Lingala, S., Kim, Y. J., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1515319 · Cited by 415 · see citing works
Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene
Mao, J.-H., Perez-losada, J., Wu, D., DelRosario, R., Tsunematsu, R., Nakayama, K. I., Brown, K., Bryson, S., & Balmain, A. (2004) · Nature · doi:10.1038/nature03155 · Cited by 390 · see citing works
Putting the stress on senescence
Serrano, M., & Blasco, M. A. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00278-7 · Cited by 413 · see citing works
Telomere dysfunction and tumour suppression: the senescence connection
Deng, Y., Chan, S. S., & Chang, S. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2393 · Cited by 411 · see citing works
Self-citationMechanisms and Regulation of Cellular Senescence
Roger, L., Tomas, F., & Gire, V. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313173 · Cited by 395 · see citing works
Cellular senescence, cancer and aging: the telomere connection
Campisi, J., Kim, S.-H., Lim, C.-S., & Rubio, M. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00160-7 · Cited by 400 · see citing works
DNA damage checkpoints in stem cells, ageing and cancer
Sperka, T., Wang, J., & Rudolph, K. L. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3420 · Cited by 393 · see citing works
Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing
Wong, K.-K., Maser, R. S., Bachoo, R. M., Menon, J., Carrasco, D. R., Gu, Y., Alt, F. W., & DePinho, R. A. (2003) · Nature · doi:10.1038/nature01385 · Cited by 375 · see citing works
Self-citationChromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers
Maser, R. S., Choudhury, B., Campbell, P. J., Feng, B., Wong, K.-K., Protopopov, A., O’Neil, J., Gutierrez, A., Ivanova, E., Perna, I., et al. (2007) · Nature · doi:10.1038/nature05886 · Cited by 377 · see citing works
Self-citationShortened Telomere Length Is Associated with Increased Risk of Cancer: A Meta-Analysis
Ma, H., Zhou, Z., Wei, S., Liu, Z., Pooley, K. A., Dunning, A. M., Svenson, U., Roos, G., Hosgood, H. D., Shen, M., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020466 · Cited by 376 · see citing works
“For example, short telomeres cause an increased risk of developing epithelial cancers by the formation of complex non-reciprocal translocations [15,16], and telomeres in tumor cells and their precursor lesions are significantly shorter than that in surrounding non-tumor cells [17,18].”
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
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
Chromosomal instability in ulcerative colitis is related to telomere shortening
O'Sullivan, J. N., Bronner, M. P., Brentnall, T. A., Finley, J. C., Shen, W.-T., Emerson, S., Emond, M. J., Gollahon, K. A., Moskovitz, A. H., Crispin, D. A., et al. (2002) · Nature Genetics · doi:10.1038/ng989 · Cited by 346 · see citing works
Aubert, G., Hills, M., & Lansdorp, P. M. (2012) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.04.003 · Cited by 342 · see citing works
DNA double strand break repair and chromosomal translocation: Lessons from animal models
Ferguson, D. O., & Alt, F. W. (2001) · Oncogene · doi:10.1038/sj.onc.1204767 · Cited by 333 · see citing works
Mechanisms that Regulate Stem Cell Aging and Life Span
Signer, R. A. J., & Morrison, S. J. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.01.001 · Cited by 320 · see citing works
Syndromes of Telomere Shortening
Armanios, M. (2009) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-082908-150046 · Cited by 317 · see citing works
Constitutive telomerase expression promotes mammary carcinomas in aging mice
Artandi, S. E., Alson, S., Tietze, M. K., Sharpless, N. E., Ye, S., Greenberg, R. A., Castrillon, D. H., Horner, J. W., Weiler, S. R., Carrasco, R. D., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.112515399 · Cited by 317 · see citing works
Self-citationPersistent 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
Telomere Length: A Review of Methods for Measurement
Montpetit, A. J., Alhareeri, A. A., Montpetit, M., Starkweather, A. R., Elmore, L. W., Filler, K., Mohanraj, L., Burton, C. W., Menzies, V. S., Lyon, D. E., et al. (2014) · Nursing Research · doi:10.1097/nnr.0000000000000037 · Cited by 293 · see citing works
The nature of telomere fusion and a definition of the critical telomere length in human cells
Capper, R., Britt-Compton, B., Tankimanova, M., Rowson, J., Letsolo, B., Man, S., Haughton, M., & Baird, D. M. (2007) · Genes & Development · doi:10.1101/gad.439107 · Cited by 294 · see citing works
Short Telomeres are Sufficient to Cause the Degenerative Defects Associated with Aging
Armanios, M., Alder, J. K., Parry, E. M., Karim, B., Strong, M. A., & Greider, C. W. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.10.028 · Cited by 257 · see citing works
Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer
Broberg, K., Björk, J., Paulsson, K., Höglund, M., & Albin, M. (2005) · Carcinogenesis · doi:10.1093/carcin/bgi063 · Cited by 255 · see citing works
Davoli, T., & de Lange, T. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.03.044 · Cited by 242 · see citing works
Telomere dysfunction provokes regional amplification and deletion in cancer genomes
O'Hagan, R. C., Chang, S., Maser, R. S., Mohan, R., Artandi, S. E., Chin, L., & DePinho, R. A. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00094-6 · Cited by 246 · see citing works
Self-citationMolecular Pathogenesis of Pancreatic Cancer
Grant, T. J., Hua, K., & Singh, A. (2016) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2016.09.008 · Cited by 237 · see citing works
Ding, Z., Wu, C.-J., Jaskelioff, M., Ivanova, E., Kost-Alimova, M., Protopopov, A., Chu, G. C., Wang, G., Lu, X., Labrot, E. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.039 · Cited by 220 · see citing works
Self-citationTelomere Dynamics in Mice and Humans
Calado, R. T., & Dumitriu, B. (2013) · Seminars in Hematology · doi:10.1053/j.seminhematol.2013.03.030 · Cited by 214 · see citing works
Assessing cell and organ senescence biomarkers
de Jesus, B. B., & Blasco, M. A. (2012) · Circulation Research · doi:10.1161/circresaha.111.247866 · Cited by 187 · see citing works
Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia
Calado, R. T., Regal, J. A., Hills, M., Yewdell, W. T., Dalmazzo, L. F., Zago, M. A., Lansdorp, P. M., Hogge, D., Chanock, S. J., Estey, E. H., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807057106 · Cited by 184 · 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
Jiang, H., Schiffer, E., Song, Z., Wang, J., Zürbig, P., Thedieck, K., Moes, S., Bantel, H., Saal, N., Jantos, J., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801457105 · Cited by 169 · see citing works
The Telomere Deprotection Response Is Functionally Distinct from the Genomic DNA Damage Response
Cesare, A. J., Hayashi, M. T., Crabbe, L., & Karlseder, J. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.06.006 · Cited by 155 · see citing works
Molecular pathogenesis of pancreatic cancer
Hansel, D. E., Kern, S. E., & Hruban, R. H. (2003) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.4.070802.110341 · Cited by 159 · see citing works
DAMPs, ageing, and cancer: The ‘DAMP Hypothesis’
Huang, J., Xie, Y., Sun, X., Zeh, H. J., Kang, R., Lotze, M. T., & Tang, D. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2014.10.004 · Cited by 144 · see citing works
Meeker, A. K., Hicks, J. L., Gabrielson, E., Strauss, W. M., De Marzo, A. M., & Argani, P. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63180-x · Cited by 140 · see citing works
Telomerase abrogation dramatically accelerates TRF2-induced epithelial carcinogenesis
Blanco, R., Muñoz, P., Flores, J. M., Klatt, P., & Blasco, M. A. (2007) · Genes & Development · doi:10.1101/gad.406207 · Cited by 135 · see citing works
Evolving views of telomerase and cancer
Blasco, M. (2003) · Trends in Cell Biology · doi:10.1016/s0962-8924(03)00085-0 · Cited by 123 · see citing works
De La Fuente, J., & Dokal, I. (2007) · Pediatric Transplantation · doi:10.1111/j.1399-3046.2007.00721.x · Cited by 119 · see citing works
ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice
Casimiro, M. C., Crosariol, M., Loro, E., Ertel, A., Yu, Z., Dampier, W., Saria, E. A., Papanikolaou, A., Stanek, T. J., Li, Z., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60256 · Cited by 115 · 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
Increased p53 activity does not accelerate telomere‐driven ageing
García‐Cao, I., García‐Cao, M., Tomás‐Loba, A., Martin‐Caballero, J., Flores, J. M., Klatt, P., Blasco, M. A., & Serrano, M. (2006) · The EMBO Reports · doi:10.1038/sj.embor.7400667 · Cited by 102 · see citing works
DePinho, R. A., & Polyak, K. (2004) · Nature Genetics · doi:10.1038/ng0904-932 · Cited by 91 · see citing works
Self-citationShort-term gain, long-term pain: the senescence life cycle and cancer
Chan, A. S. L., & Narita, M. (2019) · Genes & Development · doi:10.1101/gad.320937.118 · Cited by 80 · see citing works
Flores, I., & Blasco, M. A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004934 · Cited by 83 · see citing works
Escape from Telomere-Driven Crisis Is DNA Ligase III Dependent
Jones, R. E., Oh, S., Grimstead, J. W., Zimbric, J., Roger, L., Heppel, N. H., Ashelford, K. E., Liddiard, K., Hendrickson, E. A., & Baird, D. M. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.007 · Cited by 74 · see citing works
Alidousty, C., Baar, T., Martelotto, L. G., Heydt, C., Wagener, S., Fassunke, J., Duerbaum, N., Scheel, A. H., Frank, S., Holz, B., et al. (2018) · The Journal of Pathology · doi:10.1002/path.5110 · Cited by 69 · see citing works
Else, T., Trovato, A., Kim, A. C., Wu, Y., Ferguson, D. O., Kuick, R. D., Lucas, P. C., & Hammer, G. D. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.04.011 · Cited by 62 · see citing works
Recent advances in telomere biology: implications for human cancer
Meeker, A. K., & De Marzo, A. M. (2004) · Current Opinion in Oncology · doi:10.1097/00001622-200401000-00007 · Cited by 56 · see citing works
Telomere fusions in early human breast carcinoma
Tanaka, H., Abe, S., Huda, N., Tu, L., Beam, M. J., Grimes, B., & Gilley, D. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120062109 · Cited by 52 · see citing works
Khoo, C. M., Carrasco, D. R., Bosenberg, M. W., Paik, J.-H., & DePinho, R. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700093104 · Cited by 52 · see citing works
Self-citationHalazonetis, T. D. (2004) · DNA repair · doi:10.1016/j.dnarep.2004.03.036 · Cited by 53 · see citing works
Removing all obstacles: A critical role for p53 in promoting tissue renewal
Schoppy, D. W., Ruzankina, Y., & Brown, E. J. (2010) · Cell Cycle · doi:10.4161/cc.9.7.11194 · Cited by 32 · see citing works
Telomere fusion to chromosome breaks reduces oncogenic translocations and tumour formation
Qi, L., Strong, M. A., Karim, B. O., Huso, D. L., & Greider, C. W. (2005) · Nature Cell Biology · doi:10.1038/ncb1276 · Cited by 32 · see citing works
Reproductive aging and telomeres: Are women and men equally affected?
Chico-Sordo, L., Córdova-Oriz, I., Polonio, A. M., S-Mellado, L. S., Medrano, M., García-Velasco, J. A., & Varela, E. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111541 · Cited by 27 · see citing works
Tanaka, H., Beam, M. J., & Caruana, K. (2014) · Neoplasia · doi:10.1016/j.neo.2014.08.009 · Cited by 19 · see citing works
Telomeric 8-Oxoguanine Drives Rapid Premature Senescence In The Absence Of Telomere Shortening
Barnes, R. P., de Rosa, M., Thosar, S. A., Detwiler, A. C., Roginskaya, V., Van Houten, B., Bruchez, M. P., Stewart-Ornstein, J., & Opresko, P. L. (2021) · doi:10.1101/2021.05.05.442662
- Authors
- Artandi, S. E., Chang, S., Lee, S.-L., Alson, S., Gottlieb, G. J., Chin, L., & DePinho, R. A.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Brigham and Women's Hospital (US)
- Ackerman Academy of Dermatopathology (US)
- Harvard University (US)
- Corresponding author
- DePinho, Ronald A.
- Venue
- Nature
- Published
- 2000-08
- Volume
- 406
- Issue
- 6796
- Pages
- 641-645
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1676646253
- Semantic Scholar
- 5ea5ff3c58fa72077ce84c8ac3bbecb76b2a9ece
- Cited by
- 1,085
- References
- 8
- Citations by year
- 2026: 11 · 2025: 8 · 2024: 20 · 2023: 14 · 2022: 19 · 2021: 28 · 2020: 26 · 2019: 21 · 2018: 31 · 2017: 37 · 2016: 39 · 2015: 36 · 2014: 36 · 2013: 51 · 2012: 58
- FWCI
- 40.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation
- Universidad CES
- National Institute on Aging (K08AG001019)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- telomere dysfunction, non-reciprocal translocation, epithelial cancers, telomerase deficiency, telomere shortening, chromosomal instability, tumor suppressor, aging, carcinoma, ploidy changes, epithelial regeneration
- MeSH terms
- Adenocarcinoma, Aging, Animals, Disease Models, Animal, Female, Humans, Karyotyping, Lymphoma, Male, Mammary Neoplasms, Experimental, Mutation, Neoplasms, Glandular and Epithelial, Sarcoma, Experimental, Translocation, Genetic, Genes, p53, Telomere, Telomerase, Mice
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
