The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index.
Loss of ATRX, Genome Instability, and an Altered DNA Damage Response Are Hallmarks of the Alternative Lengthening of Telomeres Pathway
Open accessAbstract
The Alternative Lengthening of Telomeres (ALT) pathway is a telomerase-independent pathway for telomere maintenance that is active in a significant subset of human cancers and in vitro immortalized cell lines. ALT is thought to involve templated extension of telomeres through homologous recombination, but the genetic or epigenetic changes that unleash ALT are not known. Recently, mutations in the ATRX/DAXX chromatin remodeling complex and histone H3.3 were found to correlate with features of ALT in pancreatic neuroendocrine cancers, pediatric glioblastomas, and other tumors of the central nervous system, suggesting that these mutations might contribute to the activation of the ALT pathway in these cancers. We have taken a comprehensive approach to deciphering ALT by applying genomic, molecular biological, and cell biological approaches to a panel of 22 ALT cell lines, including cell lines derived in vitro. Here we show that loss of ATRX protein and mutations in the ATRX gene are hallmarks of ALT-immortalized cell lines. In addition, ALT is associated with extensive genome rearrangements, marked micronucleation, defects in the G2/M checkpoint, and altered double-strand break (DSB) repair. These attributes will facilitate the diagnosis and treatment of ALT positive human cancers.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“ALT is associated with mutations in the chromatin remodeller α-thalassaemia/mental retardation syndrome X-linked (AT R X ) both in vitro and in several human cancers, including glioblastomas162–165.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [162]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735
The DNA-damage response in human biology and disease
Jackson, S. P., & Bartek, J. (2009) · Nature · doi:10.1038/nature08467 · Cited by 6,092 · cited 1×
“The implication of ATRX and DAXX in the ALT phenotype may have some relevance to the checkpoint defects observed, as the involvement of chromatin remodelers in the DDR becomes increasingly clear [55].”
BackgroundThe landscape of somatic copy-number alteration across human cancers
Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., et al. (2010) · Nature · doi:10.1038/nature08822 · Cited by 4,017 · cited 2×
“0 algorithm was performed as previously described on the resulting segmented copy number data from the 22 ALT lines [39,59].”
BackgroundMethodSelf-citationMermel, 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 · cited 1×
“0 algorithm was performed as previously described on the resulting segmented copy number data from the 22 ALT lines [39,59].”
MethodThe Consensus Coding Sequences of Human Breast and Colorectal Cancers
Sjöblom, T., Jones, S., Wood, L. D., Parsons, D. W., Lin, J., Barber, T. D., Mandelker, D. L., Leary, R. J., Ptak, J., Silliman, N., et al. (2006) · Science · doi:10.1126/science.1133427 · Cited by 3,161
Self-citationDriver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
Schwartzentruber, J., Korshunov, A., Liu, X.-Y., Jones, D. T. W., Pfaff, E., Jacob, K., Sturm, D., Fontebasso, A. M., Quang, D.-A. K., Tönjes, M., et al. (2012) · Nature · doi:10.1038/nature10833 · Cited by 2,631 · cited 1×
“The same correlation between inactivation of the ATRX pathway and the ALT-like phenotype was observed in pediatric glioblastoma and several other cancers [16,26].”
BackgroundCounter, 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×
“In cells that have been immortalized by telomerase activation, the telomere-driven genome instability is largely dampened, resulting in a rearranged but now relatively stable karyotype [43,44].”
BackgroundJiao, Y., Shi, C., Edil, B. H., de Wilde, R. F., Klimstra, D. S., Maitra, A., Schulick, R. D., Tang, L. H., Wolfgang, C. L., Choti, M. A., et al. (2011) · Science · doi:10.1126/science.1200609 · Cited by 1,744 · cited 1×
“Recently, a subset of pancreatic neuroendocrine tumors (PanNETs) were found to have ultrabright telomeric FISH signals, suggesting the presence of ALT-like long telomeres [24,25].”
BackgroundSelf-citationTelomeric Repeat–Containing RNA and RNA Surveillance Factors at Mammalian Chromosome Ends
Azzalin, C. M., Reichenbach, P., Khoriauli, L., Giulotto, E., & Lingner, J. (2007) · Science · doi:10.1126/science.1147182 · Cited by 1,379 · cited 9×
“In addition to shelterin and TERRA, we analyzed 299 genes with potential relevance to telomeres and the ALT pathway.”
BackgroundInfluentialDistinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions
Goldberg, A. D., Banaszynski, L. A., Noh, K., Lewis, P. W., Elsässer, S. J., Stadler, S. C., Dewell, S. B., Law, M. J., Guo, X., Li, X., et al. (2010) · Cell · doi:10.1016/j.cell.2010.01.003 · Cited by 1,351
Flagged first, then by citations
1 of the 60 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 201–300 of 627
Life and cancer without telomerase: ALT and other strategies for making sure ends (don’t) meet
Apte, M. S., & Cooper, J. P. (2016) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2016.1260090 · Cited by 46
“…regulator of ALT. ALT cells show higher levels of TERRA than telomerase-positive cancer cells or primary human fibroblasts (Episkopou et al., 2014; Lovejoy et al., 2012; Schoeftner & Blasco, 2008); this increased TERRA transcription is associated with, and perhaps influenced by, hypomethylation…”
BackgroundMechanisms of Alternative Lengthening of TelomeresPreprint
O’Sullivan, R. J., & Greenberg, R. A. (2024) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041690 · Cited by 49
Fleisig, H. B., Hukezalie, K. R., Thompson, C. A. H., Au‐Yeung, T., Ludlow, A. T., Zhao, C., & Wong, J. M. Y. (2015) · Oncogene · doi:10.1038/onc.2015.75 · Cited by 42
Farooqi, A. S., Dagg, R. A., Choi, L. M. R., Shay, J. W., Reynolds, C. P., & Lau, L. M. S. (2014) · Journal of Neuro-Oncology · doi:10.1007/s11060-014-1456-8 · Cited by 42
“Although ATRX mutations and/or loss of ATRX protein expression are frequently found in ALT cell lines, 13 % of ALT cell lines express ATRX [38].”
BackgroundMost large structural variants in cancer genomes can be detected without long reads
Choo, Z.-N., Behr, J. M., Deshpande, A. S., Hadi, K., Yao, X., Tian, H., Takai, K., Zakusilo, G., Rosiene, J. A., Paula, A. D. C., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01540-6 · Cited by 40
“3c, middle) suppressed by ATRX 26 .”
Chromatin dynamics: H3K4 methylation and H3 variant replacement during development and in cancer
Deb, M., Kar, S., Sengupta, D., Shilpi, A., Parbin, S., Rath, S. K., Londhe, V. A., & Patra, S. K. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1605-4 · Cited by 43
“3 mutations are associated with ALT activation and the immortalization of cancer cells [118].”
BackgroundThe PML-Interacting Protein DAXX: Histone Loading Gets into the Picture
Salomoni, P. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00152 · Cited by 46
“, 2012) and are associated with the alternative lengthening of telomeres (ALT) mechanism (Heaphy et al., 2011; Bower et al., 2012; Liu et al., 2012; Lovejoy et al., 2012), a recombinogenic mechanism for telomere elongation.”
BackgroundIdentification of a novel gene fusion in ALT positive osteosarcoma
Mason‐Osann, E., Dai, A., Floro, J., Lock, Y. J., Reiss, M., Gali, H., Matschulat, A. M., Labadorf, A. T., & Flynn, R. L. (2018) · Oncotarget · doi:10.18632/oncotarget.26029 · Cited by 41
“19, and HUO3N1) have been characterized as ALT negative (Supplementary Figure 1, Supplementary Figure 2A–2B, and Supplementary Figure 3A–3D) [6, 20].”
BackgroundMethodInfluentialThe Chromatin Remodeler ATRX: Role and Mechanism in Biology and Cancer
Pang, Y. K., Chen, X., Ji, T., Cheng, M., Wang, R., Zhang, C., Liu, M., Zhang, J., & Zhong, C. (2023) · Cancers · doi:10.3390/cancers15082228 · Cited by 46
“A new study found that ATRX loss and mutations are hallmarks of 90% ALT-immortalized cell lines [83].”
BackgroundLee, J. C., Solomon, D. A., & Tihan, T. (2017) · Journal of Neuro-Oncology · doi:10.1007/s11060-016-2349-9 · Cited by 45
“Somatic mutations in ATRX and DAXX were initially identified in pancreatic neuroendocrine tumors [56] and were found to be highly associated with ALT [21].”
BackgroundInfluentialAlternative Lengthening of Telomeres (ALT) in Tumors and Pluripotent Stem Cells
Zhao, S., Wang, F., & Liu, L. (2019) · Genes · doi:10.3390/genes10121030 · Cited by 42
“3 is an essential step in the generation of ALT in those tumors [108], which provides potential targets for anti-cancer therapies with transgenic technology.”
BackgroundSegura‐Bayona, S., Villamor-Payà, M., Attolini, C. S., König, L. M., Sanchiz-Calvo, M., Boulton, S. J., & Stracker, T. H. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107983 · Cited by 43
de Nonneville, A. T., Salas, S., Bertucci, F., Sobinoff, A. P., Adélaı̈de, J., Guillé, A., Finetti, P., Noble, J. R., Churikov, D., Chaffanet, M., et al. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202215859 · Cited by 39
Self-citationIncorporating Advances in Molecular Pathology Into Brain Tumor Diagnostics
Vega, J. E. V., & Brat, D. J. (2018) · Advances in Anatomic Pathology · doi:10.1097/pap.0000000000000186 · Cited by 40
Rapid and reversible suppression of ALT by DAXX in osteosarcoma cells
Yost, K. E., Soper, S. F. C., Walker, R. L., Pineda, M. A., Zhu, Y. J., Ester, C. D., Showman, S., Roschke, A. V., Waterfall, J. J., & Meltzer, P. S. (2019) · Scientific Reports · doi:10.1038/s41598-019-41058-8 · Cited by 43
R-loops’ m6A modification and its roles in cancers
Qiu, Y., Man, C., Zhu, L., Zhang, S., Wang, X., Gong, D., & Fan, Y. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02148-y · Cited by 39
Morozov, V. M., Giovinazzi, S., & Ishov, A. M. (2017) · Epigenetics & Chromatin · doi:10.1186/s13072-017-0164-y · Cited by 39
Molecular markers and targeted therapy in pediatric low-grade glioma
de Blank, P. M. K., Fouladi, M., & Huse, J. T. (2020) · Journal of Neuro-Oncology · doi:10.1007/s11060-020-03529-1 · Cited by 41
Inherited germline ATRX mutation in two brothers with ATR‐X syndrome and osteosarcoma
Ji, J., Quindipan, C., Parham, D. M., Shen, L., Ruble, D., Bootwalla, M., Maglinte, D. T., Gai, X., Saitta, S. C., Biegel, J. A., et al. (2017) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.38184 · Cited by 41
“Loss of ATRX has beencorrelatedwithalternativelengtheningoftelomeres(ALT),which is associated with telomere maintenance and impaired cell growth in ALT cancer cells (Episkopou et al., 2014; Heaphy et al., 2011; Lovejoy et al., 2012; Ramamoorthy & Smith, 2015).”
BackgroundLoss of Atrx Sensitizes Cells to DNA Damaging Agents through p53-Mediated Death Pathways
Conte, D., Huh, M. S., Goodall, E. C., Delorme, M., Parks, R. J., & Picketts, D. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052167 · Cited by 40
“Furthermore, ATRX inactivation in human tumors and mouse knockout models result in abnormal telomeres [42,43,44,45].”
BackgroundResearch progress of neuroblastoma related gene variations
Cao, Y., Jin, Y., Yu, J., Wang, J., Yan, J. Y., & Zhao, Q. (2016) · Oncotarget · doi:10.18632/oncotarget.14408 · Cited by 40
“ATRX was found to be mutated in approximately 50% of adolescent and young adults with neuroblastoma [28, 92].”
BackgroundClinically relevant fusion oncogenes: detection and practical implications
Sorokin, M., Rabushko, E., Rozenberg, J. M., Mohammad, T., Seryakov, A., Sekacheva, M. I., & Buzdin, A. A. (2022) · Therapeutic Advances in Medical Oncology · doi:10.1177/17588359221144108 · Cited by 39
Lack of H3K27 trimethylation is associated with 1p/19q codeletion in diffuse gliomas
Filipski, K., Braun, Y., Zinke, J., Roller, B., Baumgarten, P., Wagner, M., Senft, C., Zeiner, P. S., Ronellenfitsch, M. W., Steinbach, J. P., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02025-9 · Cited by 36
Diagnosis and treatment of ALT tumors: is Trabectedin a new therapeutic option?
Pompili, L., Leonetti, C., Biroccio, A., & Salvati, E. (2017) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-017-0657-3 · Cited by 37
Fan, H., Chang, F.-W., Tsai, J., Lin, K., Chen, C., Lin, S., Liu, C.-A., & Harn, H. (2021) · Life · doi:10.3390/life11121405 · Cited by 39
Histone H3 Mutations in Pediatric Brain TumorsPreprint
Liu, X., McEachron, T. A., Schwartzentruber, J., & Wu, G. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a018689 · Cited by 37
“frequently observed in tumors with ATRX mutations (Lovejoy et al. 2012; Schwartzentruber et al. 2012).”
BackgroundAlternative lengthening of telomeres: mechanism and the pathogenesis of cancer
Mori, J., Keegan, J., Flynn, R. L., & Heaphy, C. M. (2023) · Journal of Clinical Pathology · doi:10.1136/jcp-2023-209005 · Cited by 35
The many facets of homologous recombination at telomeres
Claussin, C., & Chang, M. (2015) · Microbial Cell · doi:10.15698/mic2015.09.224 · Cited by 40
“3 are associated with ALT cancers (Heaphy et al., 2011; Schwartzentruber et al., 2012; Lovejoy et al., 2012; Bower et al., 2012).”
BackgroundInfluentialLoss of Telomere Protection: Consequences and Opportunities
Jacobs, J. J. L. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00088 · Cited by 40
“Interestingly, increased and ongoing chromosomal instability is also common for tumors utilizing ALT, along with telomeres that are recognized as DNAdamage, but appear not to fuse (Scheel et al., 2001; Cesare et al., 2009; Lovejoy et al., 2012).”
Telomerase and Telomeres in Endometrial Cancer
Alnafakh, R., Adishesh, M., Button, L., Saretzki, G. C., & Hapangama, D. K. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00344 · Cited by 35
“In addition, ALT is associated with marked genome rearrangements, extensive micronucleation, a defective G2/M checkpoint and alteration in double-strand break (DSB) repair (173).”
BackgroundPersistent telomere cohesion protects aged cells from premature senescence
Azarm, K., Bhardwaj, A., Kim, E., & Smith, S. H. (2020) · Nature Communications · doi:10.1038/s41467-020-17133-4 · Cited by 39
The Molecular Mechanisms and Therapeutic Prospects of Alternative Lengthening of Telomeres (ALT)
Sohn, E. J., Goralsky, J. A., Shay, J. W., & Min, J. (2023) · Cancers · doi:10.3390/cancers15071945 · Cited by 35
“Studies show that loss of ATRX also results in TERRA upregulation and G-quadruplex accumulation at telomeres [54,85].”
BackgroundBreaking new ground: Digging into TERRA function
Maicher, A., Lockhart, A., & Luke, B. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.03.012 · Cited by 37
Chromosome Evolution in Dendropsophini (Amphibia, Anura, Hylinae)
Suárez, P. X. A., Cardozo, D., Baldo, D., Pereyra, M. O., Faivovich, J., Orrico, V. G. D., Catroli, G. F., Grabiele, M., Bernarde, P. S., Nagamachi, C. Y., et al. (2013) · Cytogenetic and Genome Research · doi:10.1159/000354997 · Cited by 34
“A telomeraseindependent lengthening of the telomeres [Cheng et al., 2012; Lovejoy et al., 2012] may explain this particular phenomenon in S. lacteus , although the repetitive nature of the telomeric tandem array, which is a target of molecular alterations in the number of repetitions, is an…”
BackgroundAlternative lengthening of telomeres in molecular subgroups of paediatric high-grade glioma
Minasi, S., Baldi, C., Gianno, F., Antonelli, M., Buccoliero, A. M., Pietsch, T., Massimino, M., & Buttarelli, F. R. (2020) · Child s Nervous System · doi:10.1007/s00381-020-04933-8 · Cited by 33
A Tale of Two Tumors: Treating Pancreatic and Extrapancreatic Neuroendocrine Tumors
Halperin, D. M., Kulke, M. H., & Yao, J. C. (2014) · Annual Review of Medicine · doi:10.1146/annurev-med-061813-012908 · Cited by 34
“The impaired double-strand break repair mechanism inherent in the ALT phenotype (7) may be an appealing target for poly(ADP-ribose) polymerase (PARP) inhibition in an effort to confer synthetic lethality, potentially in combination with the alkylating agents already in use for PNETs.”
BackgroundTelomere maintenance through recruitment of internal genomic regions
Seo, B., Kim, C., Hills, M., Sung, S.-H., Kim, H., Kim, E., Lim, D. S., Oh, H., Choi, R. M. J., Chun, J., et al. (2015) · Nature Communications · doi:10.1038/ncomms9189 · Cited by 32
Graham, M. K., Kim, J. Y., Da, J., Brosnan‐Cashman, J. A., Rizzo, A. J., Valle, J. A. B.-D., Chia, L., Rubenstein, M., Davis, C., Zheng, Q., et al. (2019) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0654 · Cited by 32
“For example, ALT-positive cancer cells have defects in the G2–M checkpoint and are slow to repair double DNA breaks (21), which may, in part, explain why genes in both pathways are downregulated in LAPC-4 ATRX cells.”
BackgroundSelf-citationDisruption of ATRX-RNA interactions uncovers roles in ATRX localization and PRC2 function
Ren, W., Medeiros, N., Warneford-Thomson, R., Wulfridge, P., Yan, Q., Bian, J., Sidoli, S., Garcia, B., Skordalakes, E., Joyce, E., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15902-9 · Cited by 27
Heaphy, C. M., & Singhi, A. D. (2022) · Human Pathology · doi:10.1016/j.humpath.2022.07.015 · Cited by 35
Novakovic, B., Evain‐Brion, D., Murthi, P., Fournier, T., & Saffery, R. (2017) · The FASEB Journal · doi:10.1096/fj.201601189rr · Cited by 31
Stern, J. L., Hibshman, G. N., Hu, K., Ferrara, S. E., Costello, J. C., Kim, W., Tamayo, P., Cech, T. R., & Huang, F. W. (2020) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-1244 · Cited by 30
“Loss of E-cadherin is associated with a mesenchymal cellular state and metastasis in cancer (40,41) and significantly alters outcomes in preclinical models (42).”
BackgroundTargeting the Molecular and Immunologic Features of Leiomyosarcoma
Cope, B. M., Traweek, R. S., Lazcano, R., Keung, E. Z.-Y., Lazar, A. J., Roland, C. L., & Nassif, E. F. (2023) · Cancers · doi:10.3390/cancers15072099 · Cited by 33
“In addition to PARP inhibitor sensitivity, genomic instability resulting from DNA damage response deficiencies appears to modulate the tumor immune microenvironment.”
BackgroundInfluentialDaniloski, Z., & Smith, S. H. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-1260 · Cited by 32
ATRX and RECQ5 define distinct homologous recombination subpathways
Elbakry, A., Juhász, S., Chan, K. C., & Löbrich, M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2010370118 · Cited by 36
“3 complex, with the majority exhibiting loss of expression of the ATRX protein (41, 42).”
ALT control, delete: FANCM as an anti-cancer target in Alternative Lengthening of Telomeres
O’Rourke, J. J., Bythell‐Douglas, R., Dunn, E. A., & Deans, A. J. (2019) · Nucleus · doi:10.1080/19491034.2019.1685246 · Cited by 31
“3 are obligately mutated during the development of ALT-positive cancer [11,12].”
BackgroundMalgulwar, P. B., Danussi, C., Dharmaiah, S., Johnson, W., Singh, A. K., Rai, K., Rao, A. U. K., & Huse, J. T. (2023) · Neuro-Oncology · doi:10.1093/neuonc/noad155 · Cited by 31
Decreased Expression of the Chromatin Remodeler ATRX Associates with Melanoma Progression
Qadeer, Z. A., Harcharik, S., Valle‐García, D., Chen, C., Birgé, M. B., Vardabasso, C., Duarte, L. F., & Bernstein, E. (2014) · Journal of Investigative Dermatology · doi:10.1038/jid.2014.45 · Cited by 29
“Because structural variations of ATRX exist in neuroblastoma and osteosarcoma (Cheung et al., 2012; Lovejoy et al., 2012), we determined whether such alterations are present in metastatic melanoma.”
BackgroundMethodChow, T. T., Shi, X., Wei, J., Guan, J., Stadler, G., Huang, B., & Blackburn, E. H. (2018) · Nature Communications · doi:10.1038/s41467-018-05840-y · Cited by 32
Expression of tert Prevents ALT in Zebrafish Brain Tumors
Idilli, A. I., Cusanelli, E., Pagani, F., Kerschbamer, E., Berardinelli, F., Bernabe, M., Cayuela, M. L., Piazza, S., Poliani, P. L., & Mione, M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00065 · Cited by 28
Wang, F., Xu, X., Zeng, Y., Qin, Y., Yu, X., & Ji, S. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.691557 · Cited by 30
Hypo-methylation mediates chromosomal instability in pancreatic NET
Marinoni, I., Wiederkeher, A., Wiedmer, T., Pantasis, S., Domenico, A. D., Frank, R. M., Vassella, E., Schmitt, A. M., & Perren, A. A. (2017) · Endocrine Related Cancer · doi:10.1530/erc-16-0554 · Cited by 34
Marcomini, I., Shimada, K., Delgoshaie, N., Yamamoto, I., Seeber, A., Cheblal, A., Horigome, C., Naumann, U., & Gasser, S. M. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.102 · Cited by 30
Onciul, R., Brehar, F.-M., Toader, C., Covache-Busuioc, R.-A., Glavan, L.-A., Bratu, B.-G., Costin, H. P., Dumitrascu, D.-I., Șerban, M., & Ciurea, A. V. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46030153 · Cited by 30
Gastroenteropancreatic endocrine tumors
Meeker, A. K., & Heaphy, C. M. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.07.015 · Cited by 31
“Similarly, Lovejoy et al. compared several ALT-positive clonal sublines to their ALT-negative parental cells of origin and found a strong association between ATRX mutations and ALT (Lovejoy et al., 2012).”
BackgroundSelf-citationEpigenetic Regulation of Telomere Maintenance for Therapeutic Interventions in Gliomas
Naderlinger, E., & Holzmann, K. (2017) · Genes · doi:10.3390/genes8050145 · Cited by 31
“ALT in tumor derived cell lines and immortalized fibroblasts is associated with extreme long and heterogeneous telomeres, defects in the G2/M checkpoint of the cell cycle and reduced capability of double-strand break repair [54].”
BackgroundAlternative Lengthening of Telomeres in Pediatric Cancer: Mechanisms to Therapies
Kent, T., Gracias, D., Shepherd, S., & Clynes, D. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2019.01518 · Cited by 29
“ALT cancers also display increased replicative stress and telomeric DNA damage induced foci (TIFs), a potential driver of ALT generation (18, 19).”
BackgroundChen, Y., Dagg, R. A., Zhang, Y., Lee, J. H. Y., Lu, R., Rotta, N. M. L., Sampl, S., Korkut-Demirbaş, M., Holzmann, K., Lau, L. M. S., et al. (2021) · Cancers · doi:10.3390/cancers13215369 · Cited by 28
“Both telomeres that are too short to be functional and those that are too long to avoid replication fork stalling could be sources of the increased DNA damage signals seen in the ALT+ telomeres [9,10].”
BackgroundSelf-citationDeWitt, S. B., Plumlee, S. H., Brighton, H. E., Sivaraj, D., Martz, E. J., Zand, M., Kumar, V., Sheth, M. U., Floyd, W., Spruance, J., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.151583 · Cited by 29
“In the context of cancers, nearly all published studies have focused on the correlation between loss of ATRX expression and activation of the alternative lengthening of telomeres (ALT) pathway for telomere maintenance (21, 22, 29, 30).”
BackgroundRNA–DNA Hybrids Support Recombination-Based Telomere Maintenance in Fission Yeast
Hu, Y., Bennett, H. W., Liu, N., Moravec, M., Williams, J. F., Azzalin, C. M., & King, M. C. (2019) · Genetics · doi:10.1534/genetics.119.302606 · Cited by 31
Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs
Rosso, I., Jones-Weinert, C. W., Rossiello, F., Cabrini, M., Brambillasca, S., Muñoz‐Sagredo, L., Lavagnino, Z., Martini, E., Tedone, E., Garrè, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42831-0 · Cited by 28
“…to be a component of the ALT pathway, as inactivating mutations in the cooperating histone chaperones ATRX and DAXX are associated with ALT 35,36 where they contribute to increased sister chromatid cohesion and multiple ALT hallmarks including APBs, C-circles, T-SCE, as well as telomere…”
BackgroundShastrula, P. K., Sierra, I., Deng, Z., Keeney, F., Hayden, J. E., Lieberman, P. M., & Janicki, S. M. (2019) · Journal of Cell Science · doi:10.1242/jcs.220970 · Cited by 34
“However, when the array is integrated into U2OS cells, which are ATRX-null and use the alternative lengthening of telomere (ALT) pathway instead of telomerase to maintain telomere length (Lovejoy et al., 2012), H3.”
BackgroundTelomeres in toxicology: Occupational health
Shoeb, M., Meier, H. C. S., & Antonini, J. M. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107742 · Cited by 32
Oncogenic herpesvirus KSHV triggers hallmarks of alternative lengthening of telomeres
Lippert, T. P., Marzec, P., Idilli, A. I., Sarek, G., Vančevska, A., Bower, M., Farrell, P. J., Ojala, P. M., Feldhahn, N., & Boulton, S. J. (2021) · Nature Communications · doi:10.1038/s41467-020-20819-4 · Cited by 27
ATRX proximal protein associations boast roles beyond histone deposition
Scott, W. A., Dhanji, E. Z., Dyakov, B. J. A., Dreseris, E. S., Jonathon, S., Grange, L. J., Mirceta, M., Pearson, C. E., Stewart, G. S., Gingras, A., et al. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009909 · Cited by 27
Functions of ADP-ribose transferases in the maintenance of telomere integrity
Muoio, D., Laspata, N., & Fouquerel, E. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04235-z · Cited by 34
Turkalo, T. K., Maffia, A., Schabort, J. J., Regalado, S. G., Bhakta, M. S., Blanchette, M., Spierings, D. C. J., Lansdorp, P. M., & Hockemeyer, D. F. (2023) · Nature Communications · doi:10.1038/s41467-023-36294-6 · Cited by 30
Sakellariou, D., Chiourea, M., Raftopoulou, C., & Gagos, S. (2013) · Neoplasia · doi:10.1593/neo.131574 · Cited by 28
“In addition, the ALT cells take advantage of high rates of endogenous CIN and undergo selection adaptation processes that shape their genome toward the depletion of several regulators of the epigenome such as ATRX and DAXX [29,117].”
BackgroundResultInfluentialGocha, A. R. S., Harris, J. M., & Groden, J. L. (2012) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2012.11.006 · Cited by 28
“DAXX expression is low or undetectable in 4 of the 22 ALT cell lines, although no mutations or deletions were identified in DAXX [51].”
Wei, J. S., Johansson, P. A., Chen, L., Song, Y., Tolman, C., Li, S., Hurd, L., Patidar, R., Wen, X., Badgett, T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077731 · Cited by 27
“cancers [39-41].”
The Genome of the Chicken DT40 Bursal Lymphoma Cell Line
Molnár, J., Póti, Á., Pipek, O., Krzystanek, M., Kanu, N., Swanton, C., Tusnády, G., Szállási, Z., Csabai, I., & Szüts, D. (2014) · G3 Genes Genomes Genetics · doi:10.1534/g3.114.013482 · Cited by 28
Tang, M., Li, Y., Zhang, Y., Chen, Y., Huang, W., Wang, D., Zaug, A. J., Liu, D., Zhao, Y. B., Cech, T. R., et al. (2014) · Journal of Cell Science · doi:10.1242/jcs.159467 · Cited by 27
“3 mutations have been found primarily in telomerase-negative ALT cancers (Heaphy et al., 2011; Lovejoy et al., 2012; Schwartzentruber et al., 2012), DAXX mutations are seen in both telomerasepositive and -negative cancers.”
BackgroundMethodMeans to the ends: The role of telomeres and telomere processing machinery in metastasis
Robinson, N. J., & Schiemann, W. P. (2016) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2016.10.005 · Cited by 28
“Activation of DDRs occurs in response to telomere shortening, thereby reducing the degree of telomere protection by shelterin complexes [80].”
BackgroundInfluentialBoroujeni, A. M., Kertowidjojo, E. C., Wu, X., Soslow, R. A., Chiang, S., da Silva, E. M., Weigelt, B., & Chui, M. H. (2022) · Modern Pathology · doi:10.1038/s41379-022-01160-1 · Cited by 27
Induction of the alternative lengthening of telomeres pathway by trapping of proteins on DNA
Rose, A. M., Goncalves, T., Cunniffe, S. M. T., Geiller, H. E. B., Kent, T., Shepherd, S., Ratnaweera, M., O’Sullivan, R. J., Gibbons, R. J., & Clynes, D. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad150 · Cited by 29
Liquid biopsy: creating opportunities in brain space
Trivedi, R., & Bhat, K. P. (2023) · British Journal of Cancer · doi:10.1038/s41416-023-02446-0 · Cited by 27
ATRX driver mutation in a composite malignant pheochromocytoma
Comino‐Méndez, I., Tejera, Á. M., Currás-Freixes, M., Remacha, L., Gonzálvo, P., Tonda, R., Letón, R., Blasco, M. A., Robledo, M., & Cascón, A. (2016) · Cancer Genetics · doi:10.1016/j.cancergen.2016.04.058 · Cited by 29
Telomerase and Telomeres Biology in Thyroid Cancer
Donati, B., & Ciarrocchi, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20122887 · Cited by 29
Diverging RNPs: Toward Understanding lncRNA-Protein Interactions and Functions
Sauvageau, M. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-31434-7_10 · Cited by 27
R-Loops and Its Chro-Mates: The Strange Case of Dr. Jekyll and Mr. Hyde
Uruci, S., Lo, C. S. Y., Wheeler, D. L., & Taneja, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168850 · Cited by 26
R-Loops at Chromosome Ends: From Formation, Regulation, and Cellular Consequence
Gong, Y., & Liu, Y. (2023) · Cancers · doi:10.3390/cancers15072178 · Cited by 31
“A systematic test of ATRX expression in 22 human ALT cell lines has revealed that 19 out of 22 lines have lower or complete loss of ATRX expression [78].”
BackgroundFloyd, W., Pierpoint, M., Su, C., Patel, R., Luo, L., Deland, K., Wisdom, A. J., Zhu, D., Ma, Y., DeWitt, S. B., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci149310 · Cited by 28
“In conjunction with previously published work (9, 11, 21, 22), these findings motivated us to generate a mouse model of Atrx-deleted sarcoma and examine the response to DNA DSB–inducing therapeutics.”
RNase P protein subunit Rpp29 represses histone H3.3 nucleosome deposition
Newhart, A., Powers, S. L., Shastrula, P. K., Sierra, I., Joo, L. M., Hayden, J. E., Cohen, A. R., & Janicki, S. M. (2016) · Molecular Biology of the Cell · doi:10.1091/mbc.e15-02-0099 · Cited by 26
“Loss of ATRX is a hallmark of cells, including U2OS, that use the alternative lengthening of telomere (ALT) pathway to maintain telomere length (Heaphy et al., 2011; Bower et al., 2012; Lovejoy et al., 2012).”
BackgroundDifferential nuclear ATRX expression in sarcomas
Koelsche, C., Renner, M., Johann, P. D., Leiss, I., Sahm, F., Schimmack, S. J., Wardelmann, E., Renker, E.-K., Schirmacher, P., Korshunov, A., et al. (2015) · Histopathology · doi:10.1111/his.12812 · Cited by 25
“Structural variations of ATRX have been described in neuroblastomas and osteosarcomas.(13,38) Furthermore, transcriptional repression rather than ATRX mutations or structural variations caused loss of ATRX expression in progressed melanomas.”
BackgroundInfluentialCompromised Telomeric Heterochromatin Promotes ALTernative Lengthening of Telomeres
Voon, H. P. J., Collas, P., & Wong, L. H. (2016) · Trends in cancer · doi:10.1016/j.trecan.2016.02.003 · Cited by 26
“3 at telomeres [2,3], are frequent in ALT-dependent cancers [4–7] (Box 1).”
BackgroundLarge variety in a panel of human colon cancer organoids in response to EZH2 inhibition
Koppens, M. A. J., Bounova, G., Cornelissen‐Steijger, P., de Vries, N., Sansom, O. J., Wessels, L. F. A., & van Lohuizen, M. (2016) · Oncotarget · doi:10.18632/oncotarget.12002 · Cited by 27
Ferreira, M. S. V., Sørensen, M. D., Pusch, S., Beier, D., Bouillon, A., Kristensen, B. W., Brümmendorf, T. H., Beier, C. P., & Beier, F. (2020) · Journal of Neuro-Oncology · doi:10.1007/s11060-020-03394-y · Cited by 25
Mechanisms of Nucleosome Dynamics In VivoPreprint
Henikoff, S. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026666 · Cited by 27
“A unique feature of ATRX and DAXX mutations is that they are hallmarks of the alternative lengthening of telomeres (ALT) phenotype (Lovejoy et al. 2012).”
BackgroundPan-Cancer Analysis of Alternative Lengthening of Telomere Activity
Sung, J., Lim, H., Joung, J., & Park, W. (2020) · Cancers · doi:10.3390/cancers12082207 · Cited by 26
“In addition, ALT-positive tumors have recurrent mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene [15] and the gene encoding the death domain associated (DAXX) protein [16].”
BackgroundTimpano, S., & Picketts, D. J. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00885 · Cited by 28
Macha, S. J., Koneru, B., Burrow, T. A., Zhu, C., Savitski, D., Rahman, R. L., Ronaghan, C. A., Nance, J., McCoy, K., Eslinger, C. R., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-0125 · Cited by 24
Oncohistones and disrupted development in pediatric-type diffuse high-grade glioma
Ocasio, J. K., Budd, K. M., Roach, J. T., Andrews, J. M., & Baker, S. J. (2023) · Cancer and Metastasis Reviews · doi:10.1007/s10555-023-10105-2 · Cited by 27
Mre11 and Blm-Dependent Formation of ALT-Like Telomeres in Ku-Deficient Ustilago maydis
Yu, E. Y., Pérez‐Martín, J., Holloman, W. K., & Lue, N. F. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005570 · Cited by 25
Self-citationALT: A Multi-Faceted Phenomenon
Sommer, A., & Royle, N. J. (2020) · Genes · doi:10.3390/genes11020133 · Cited by 25
“ATRX inactivation can be the result point mutations, small or large deletions but also by mutations n t readily detected by sequen e analysis such as translocations or promoter silencing mutations, but resulting nonetheless in oss of protein xpression [70].”
BackgroundInfluentialReading between the Lines: “ADD”-ing Histone and DNA Methylation Marks toward a New Epigenetic “Sum”
Noh, K., Allis, C. D., & Li, H. (2015) · ACS Chemical Biology · doi:10.1021/acschembio.5b00830 · Cited by 26
Kunieda, J., Yamashita, K., Togashi, Y., Baba, S., Sakata, S., Inamura, K., Ae, K., Matsumoto, S., Machinami, R., Kitagawa, M., et al. (2021) · Cancer Science · doi:10.1111/cas.15256 · Cited by 23
XPF activates break-induced telomere synthesis
Guh, C.-Y., Shen, H.-J., Chen, L. W., Chiu, P.-C., Liao, I.-H., Lo, C.-C., Chen, Y., Hsieh, Y.-H., Chang, T.-C., Yen, C.-P., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33428-0 · Cited by 25
Li, F., Wang, Y., Hwang, I., Jang, J.-Y., Xu, L., Deng, Z., Yu, E. Y., Cai, Y., Wu, C., Han, Z., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37480-2 · Cited by 25
Self-citationTelomere-lengthening mechanism revealed
Roake, C. M., & Artandi, S. E. (2016) · Nature · doi:10.1038/nature19483 · Cited by 25
Young, C. C., Baker, R. M., Howlett, C. J., Hryciw, T., Herman, J. E., Higgs, D. R., Gibbons, R. J., Crawford, H. C., Brown, A. M., & Pin, C. L. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.09.004 · Cited by 23
Metadata
- Authors
- Lovejoy, C. A., Li, W., Reisenweber, S., Thongthip, S., Bruno, J., de Lange, T., De, S., Petrini, J. H. J., Sung, P. A., Jasin, M., Rosenbluh, J., Zwang, Y., Weir, B. A., Hatton, C., Ivanova, E., Macconaill, L., Hanna, M., Hahn, W. C., Lue, N. F., Reddel, R. R., Jiao, Y., Kinzler, K., Vogelstein, B., Papadopoulos, N., Meeker, A. K., & for the ALT Starr Cancer Consortium
- Affiliations
- Rockefeller University (US)
- Memorial Sloan Kettering Cancer Center (US)
- Broad Institute (US)
- Dana-Farber Cancer Institute (US)
- Cornell University (US)
- The University of Sydney (AU)
- Johns Hopkins University (US)
- ORCID
- Lovejoy, Courtney A.
- Thongthip, Supawat
- Bruno, Joanne
- De, Saurav
- Petrini, John H. J.
- Sung, Patricia A.
- Jasin, Maria
- Rosenbluh, Joseph
- Zwang, Yaara
- Hatton, Charlie
- Ivanova, Elena
- Macconaill, Laura
- Hahn, William C.
- Lue, Neal F.
- Reddel, Roger R.
- Jiao, Yuchen
- Kinzler, Kenneth
- Vogelstein, Bert
- Papadopoulos, Nickolas
- Meeker, Alan K.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-07-19
- Volume
- 8
- Issue
- 7
- Pages
- e1002772
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC3400581
- OpenAlex
- W1999626396
- Cited by
- 629
- References
- 60
- Citations by year
- 2026: 34 · 2025: 41 · 2024: 33 · 2023: 44 · 2022: 51 · 2021: 52 · 2020: 49 · 2019: 54 · 2018: 53 · 2017: 44 · 2016: 41 · 2015: 49 · 2014: 44 · 2013: 33 · 2012: 6
- FWCI
- 28.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- U.S. Department of Defense
- National Institutes of Health
- Cancer Council NSW
- National Institute on Aging (R01AG023145)
- National Cancer Institute (CA076027, R01CA076027, R37CA043460, R13CA162528)
- National Institute of General Medical Sciences (R37GM059413, R37GM049046, R01GM049046, F32GM090437, GM049046, R01GM056888)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- alternative lengthening of telomeres, ATRX, histone H3.3, genomic instability, DNA damage response, DNA double-strand break repair, G2/M checkpoint, micronucleation, genome rearrangement, telomere maintenance
- MeSH terms
- X-linked Nuclear Protein, DNA Damage, DNA Repair, DNA Helicases, HeLa Cells, Histones, Humans, Nuclear Proteins, Signal Transduction, Telomere, Molecular Chaperones, Telomerase, Chromatin Assembly and Disassembly, Genomic Instability, Adaptor Proteins, Signal Transducing, DNA Breaks, Double-Stranded, Co-Repressor Proteins, Telomere Homeostasis, G2 Phase Cell Cycle Checkpoints, Homologous Recombination
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
