Presence of TERT Promoter Mutations is a Secondary Event and Associates with Elongated Telomere Length in Myxoid Liposarcomas.

Ferreira, Monica S. Ventura; Crysandt, Martina; Braunschweig, Till; Jost, Edgar; Voss, Barbara; Bouillon, Anne-Sophie; Knuechel, Ruth; Brummendorf, Tim H.; Beier, Fabian

doi:10.3390/ijms19020608

Article (Scientific journals)

Presence of TERT Promoter Mutations is a Secondary Event and Associates with Elongated Telomere Length in Myxoid Liposarcomas.

Ferreira, Monica S. Ventura; Crysandt, Martina; Braunschweig, Till et al.

2018 • In International Journal of Molecular Sciences, 19 (2)

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/246789

DOI
10.3390/ijms19020608

PubMed
29463038

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Keywords :

Base Sequence; Bone Neoplasms/genetics; Female; Humans; In Situ Hybridization, Fluorescence; Liposarcoma, Myxoid/genetics; Male; Middle Aged; Mutation/genetics; Neoplasm Grading; Promoter Regions, Genetic; Sarcoma/genetics; Telomerase/genetics; Telomere/metabolism; TERT promoter mutation; myxoid liposarcoma; sarcoma; telomerase; telomere

Abstract :

[en] The occurrence of TERT promoter mutations has been well described in soft tissue sarcomas (STS). However, the biological role of these mutations as well as their impact on telomere length in STS is still unclear. We analyzed 116 patient samples diagnosed with 22 distinct histological subtypes of bone and STS for the occurrence of TERT promoter mutations by Sanger sequencing. We observed TERT promoter mutations at an overall frequency of 9.5% distributed over 7 different sarcoma subtypes. Except for one chondrosarcoma case harboring a C250T mutation, all other mutations were detected at location C228T. By far the far highest frequency of TERT promoter mutations was found in myxoid liposarcoma (MLS) (4 out of 9 cases studied, i.e., 44%). Assessment of telomere length from tumor biopsies revealed that TERT promoter-mutated MLSs had significantly fewer shortened telomeres in comparison to TERT wildtype MLSs. Based on the frequency of TERT promoter mutations and the elongated telomere length in mutated compared to wildtype MLS, we hypothesize that occurrence of TERT promoter mutations has a pivotal role in the disease progression as a secondary genetic event at a time when tumor cells face the need for telomere elongation to allow further proliferation.

Disciplines :

Hematology

Author, co-author :

Ferreira, Monica S. Ventura

Crysandt, Martina

Braunschweig, Till

Jost, Edgar

Voss, Barbara

Bouillon, Anne-Sophie ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service d'hématologie clinique

Knuechel, Ruth

Brummendorf, Tim H.

Beier, Fabian

Language :

English

Title :

Presence of TERT Promoter Mutations is a Secondary Event and Associates with Elongated Telomere Length in Myxoid Liposarcomas.

Publication date :

2018

Journal title :

International Journal of Molecular Sciences

ISSN :

1661-6596

eISSN :

1422-0067

Publisher :

Multidisciplinary Digital Publishing Institute (MDPI), Switzerland

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 22 April 2020

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Bibliography

De Lange, T. Protection of mammalian telomeres. Oncogene 2002, 21, 532–540.
Hayflick, L. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 1965, 37, 614–636.
Bodnar, A.G.; Ouellette, M.; Frolkis, M.; Holt, S.E.; Chiu, C.P.; Morin, G.B.; Harley, C.B.; Shay, J.W.; Lichtsteiner, S.; Wright, W.E. Extension of life-span by introduction of telomerase into normal human cells. Science 1998, 279, 349–352.
Morales, C.P.; Holt, S.E.; Ouellette, M.; Kaur, K.J.; Yan, Y.; Wilson, K.S.; White, M.A.; Wright, W.E.; Shay, J.W. Absence of cancer-associated changes in human fibroblasts immortalized with telomerase. Nat. Genet. 1999, 21, 115–118.
Ziegler, P.; Schrezenmeier, H.; Akkad, J.; Brassat, U.; Vankann, L.; Panse, J.; Wilop, S.; Balabanov, S.; Schwarz, K.; Martens, U.M.; et al. Telomere elongation and clinical response to androgen treatment in a patient with aplastic anemia and a heterozygous htert gene mutation. Ann. Hematol. 2012, 91, 1115–1120.
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674.
Kim, N.W.; Piatyszek, M.A.; Prowse, K.R.; Harley, C.B.; West, M.D.; Ho, P.L.; Coviello, G.M.; Wright, W.E.; Weinrich, S.L.; Shay, J.W. Specific association of human telomerase activity with immortal cells and cancer. Science 1994, 266, 2011–2015.
Bryan, T.M.; Englezou, A.; Dalla-Pozza, L.; Dunham, M.A.; Reddel, R.R. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat. Med. 1997, 3, 1271–1274.
Ropio, J.; Merlio, J.P.; Soares, P.; Chevret, E. Telomerase activation in hematological malignancies. Genes 2016, 7, 61.
Horn, S.; Figl, A.; Rachakonda, P.S.; Fischer, C.; Sucker, A.; Gast, A.; Kadel, S.; Moll, I.; Nagore, E.; Hemminki, K.; et al. Tert promoter mutations in familial and sporadic melanoma. Science 2013, 339, 959– 961.
Huang, F.W.; Hodis, E.; Xu, M.J.; Kryukov, G.V.; Chin, L.; Garraway, L.A. Highly recurrent tert promoter mutations in human melanoma. Science 2013, 339, 957–959.
Vinagre, J.; Almeida, A.; Populo, H.; Batista, R.; Lyra, J.; Pinto, V.; Coelho, R.; Celestino, R.; Prazeres, H.; Lima, L.; et al. Frequency of tert promoter mutations in human cancers. Nat. Commun. 2013, 4, 2185.
Killela, P.J.; Reitman, Z.J.; Jiao, Y.; Bettegowda, C.; Agrawal, N.; Diaz, L.A., Jr.; Friedman, A.H.; Friedman, H.; Gallia, G.L.; Giovanella, B.C.; et al. Tert promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc. Natl. Acad. Sci. USA 2013, 110, 6021–6026.
Heidenreich, B.; Rachakonda, P.S.; Hemminki, K.; Kumar, R. Tert promoter mutations in cancer development. Curr. Opin. Genet. Dev. 2014, 24, 30–37.
Liu, T.; Yuan, X.; Xu, D. Cancer-specific telomerase reverse transcriptase (tert) promoter mutations: Biological and clinical implications. Genes 2016, 7, 38.
Bell, R.J.; Rube, H.T.; Xavier-Magalhaes, A.; Costa, B.M.; Mancini, A.; Song, J.S.; Costello, J.F. Understanding tert promoter mutations: A common path to immortality. Mol. Cancer Res. MCR 2016, 14, 315–323.
Chibon, F.; Lagarde, P.; Salas, S.; Perot, G.; Brouste, V.; Tirode, F.; Lucchesi, C.; de Reynies, A.; Kauffmann, A.; Bui, B.; et al. Validated prediction of clinical outcome in sarcomas and multiple types of cancer on the basis of a gene expression signature related to genome complexity. Nat. Med. 2010, 16, 781–787.
Rieker, R.J.; Weitz, J.; Lehner, B.; Egerer, G.; Mueller, A.; Kasper, B.; Schirmacher, P.; Joos, S.; Mechtersheimer, G. Genomic profiling reveals subsets of dedifferentiated liposarcoma to follow separate molecular pathways. Virchows Arch. Int. J. Pathol. 2010, 456, 277–285.
Segal, N.H.; Pavlidis, P.; Antonescu, C.R.; Maki, R.G.; Noble, W.S.; DeSantis, D.; Woodruff, J.M.; Lewis, J.J.; Brennan, M.F.; Houghton, A.N.; et al. Classification and subtype prediction of adult soft tissue sarcoma by functional genomics. Am. J. Pathol. 2003, 163, 691–700.
De Alava, E. Molecular pathology in sarcomas. Clin. Transl. Oncol. 2007, 9, 130–144.
Ron, D.; Habener, J.F. Chop, a novel developmentally regulated nuclear protein that dimerizes with transcription factors c/ebp and lap and functions as a dominant-negative inhibitor of gene transcription. Genes Dev. 1992, 6, 439–453.
Fornace, A.J., Jr.; Nebert, D.W.; Hollander, M.C.; Luethy, J.D.; Papathanasiou, M.; Fargnoli, J.; Holbrook, N.J. Mammalian genes coordinately regulated by growth arrest signals and DNA-damaging agents. Mol. Cell. Biol. 1989, 9, 4196–4203.
Goransson, M.; Andersson, M.K.; Forni, C.; Stahlberg, A.; Andersson, C.; Olofsson, A.; Mantovani, R.; Aman, P. The myxoid liposarcoma fus-ddit3 fusion oncoprotein deregulates nf-kappab target genes by interaction with nfkbiz. Oncogene 2009, 28, 270–278.
Riggi, N.; Cironi, L.; Provero, P.; Suva, M.L.; Stehle, J.C.; Baumer, K.; Guillou, L.; Stamenkovic, I. Expression of the fus-chop fusion protein in primary mesenchymal progenitor cells gives rise to a model of myxoid liposarcoma. Cancer Res. 2006, 66, 7016–7023.
Perez-Losada, J.; Pintado, B.; Gutierrez-Adan, A.; Flores, T.; Banares-Gonzalez, B.; del Campo, J.C.; Martin-Martin, J.F.; Battaner, E.; Sanchez-Garcia, I. The chimeric fus/tls-chop fusion protein specifically induces liposarcomas in transgenic mice. Oncogene 2000, 19, 2413–2422.
Perez-Losada, J.; Sanchez-Martin, M.; Rodriguez-Garcia, M.A.; Perez-Mancera, P.A.; Pintado, B.; Flores, T.; Battaner, E.; Sanchez-Garcia, I. Liposarcoma initiated by fus/tls-chop: The fus/tls domain plays a critical role in the pathogenesis of liposarcoma. Oncogene 2000, 19, 6015–6022.
Avigad, S.; Naumov, I.; Ohali, A.; Jeison, M.; Berco, G.H.; Mardoukh, J.; Stark, B.; Ash, S.; Cohen, I.J.; Meller, I.; et al. Short telomeres: A novel potential predictor of relapse in ewing sarcoma. Clin. Cancer Res. 2007, 13, 5777–5783.
Xie, H.; Wu, X.; Wang, S.; Chang, D.; Pollock, R.E.; Lev, D.; Gu, J. Long telomeres in peripheral blood leukocytes are associated with an increased risk of soft tissue sarcoma. Cancer 2013, 119, 1885–1891.
Montgomery, E.; Argani, P.; Hicks, J.L.; DeMarzo, A.M.; Meeker, A.K. Telomere lengths of translocation-associated and nontranslocation-associated sarcomas differ dramatically. Am. J. Pathol. 2004, 164, 1523– 1529.
Jeyapalan, J.N.; Mendez-Bermudez, A.; Zaffaroni, N.; Dubrova, Y.E.; Royle, N.J. Evidence for alternative lengthening of telomeres in liposarcomas in the absence of alt-associated pml bodies. Int. J. Cancer 2008, 122, 2414–2421.
Henson, J.D.; Hannay, J.A.; McCarthy, S.W.; Royds, J.A.; Yeager, T.R.; Robinson, R.A.; Wharton, S.B.; Jellinek, D.A.; Arbuckle, S.M.; Yoo, J.; et al. A robust assay for alternative lengthening of telomeres in tumors shows the significance of alternative lengthening of telomeres in sarcomas and astrocytomas. Clin. Cancer Res. 2005, 11, 217–225.
Liau, J.Y.; Tsai, J.H.; Jeng, Y.M.; Lee, J.C.; Hsu, H.H.; Yang, C.Y. Leiomyosarcoma with alternative lengthening of telomeres is associated with aggressive histologic features, loss of atrx expression, and poor clinical outcome. Am. J. Surg. Pathol. 2015, 39, 236–244.
Lee, J.C.; Jeng, Y.M.; Liau, J.Y.; Tsai, J.H.; Hsu, H.H.; Yang, C.Y. Alternative lengthening of telomeres and loss of atrx are frequent events in pleomorphic and dedifferentiated liposarcomas. Mod. Pathol. 2015, 28, 1064–1073.
Costa, A.; Daidone, M.G.; Daprai, L.; Villa, R.; Cantu, S.; Pilotti, S.; Mariani, L.; Gronchi, A.; Henson, J.D.; Reddel, R.R.; et al. Telomere maintenance mechanisms in liposarcomas: Association with histologic subtypes and disease progression. Cancer Res. 2006, 66, 8918–8924.
Gocha, A.R.; Nuovo, G.; Iwenofu, O.H.; Groden, J. Human sarcomas are mosaic for telomerase-dependent and telomerase-independent telomere maintenance mechanisms: Implications for telomere-based therapies. Am. J. Pathol. 2013, 182, 41–48.
Johnson, J.E.; Varkonyi, R.J.; Schwalm, J.; Cragle, R.; Klein-Szanto, A.; Patchefsky, A.; Cukierman, E.; von Mehren, M.; Broccoli, D. Multiple mechanisms of telomere maintenance exist in liposarcomas. Clin. Cancer Res. 2005, 11, 5347–5355.
Saito, T.; Akaike, K.; Kurisaki-Arakawa, A.; Toda-Ishii, M.; Mukaihara, K.; Suehara, Y.; Takagi, T.; Kaneko, K.; Yao, T. Tert promoter mutations are rare in bone and soft tissue sarcomas of japanese patients. Mol. Clin. Oncol. 2016, 4, 61–64.
Koelsche, C.; Renner, M.; Hartmann, W.; Brandt, R.; Lehner, B.; Waldburger, N.; Alldinger, I.; Schmitt, T.; Egerer, G.; Penzel, R.; et al. Tert promoter hotspot mutations are recurrent in myxoid liposarcomas but rare in other soft tissue sarcoma entities. J. Exp. Clin. Cancer Res. CR 2014, 33, 33.
Campanella, N.C.; Penna, V.; Abrahao-Machado, L.F.; Cruvinel-Carloni, A.; Ribeiro, G.; Soares, P.; Scapulatempo-Neto, C.; Reis, R.M. Tert promoter mutations in soft tissue sarcomas. Int. J. Biol. Markers 2016, 31, e62–e67.
Chiba, K.; Johnson, J.Z.; Vogan, J.M.; Wagner, T.; Boyle, J.M.; Hockemeyer, D. Cancer-associated tert promoter mutations abrogate telomerase silencing. eLife 2015, 4, e07918.
Kinde, I.; Munari, E.; Faraj, S.F.; Hruban, R.H.; Schoenberg, M.; Bivalacqua, T.; Allaf, M.; Springer, S.; Wang, Y.; Diaz, L.A., Jr.; et al. Tert promoter mutations occur early in urothelial neoplasia and are biomarkers of early disease and disease recurrence in urine. Cancer Res. 2013, 73, 7162–7167.
Wang, N.; Liu, T.; Sofiadis, A.; Juhlin, C.C.; Zedenius, J.; Hoog, A.; Larsson, C.; Xu, D. Tert promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (fta) and atypical fta. Cancer 2014, 120, 2965–2979.
Hosler, G.A.; Davoli, T.; Mender, I.; Litzner, B.; Choi, J.; Kapur, P.; Shay, J.W.; Wang, R.C. A primary melanoma and its asynchronous metastasis highlight the role of braf, cdkn2a, and tert. J. Cutan. Pathol. 2015, 42, 108–117.
Shain, A.H.; Yeh, I.; Kovalyshyn, I.; Sriharan, A.; Talevich, E.; Gagnon, A.; Dummer, R.; North, J.; Pincus, L.; Ruben, B.; et al. The genetic evolution of melanoma from precursor lesions. N. Engl. J. Med. 2015, 373, 1926–1936.
Scott, G.A.; Laughlin, T.S.; Rothberg, P.G. Mutations of the tert promoter are common in basal cell carcinoma and squamous cell carcinoma. Mod. Pathol. 2014, 27, 516–523.
Arita, H.; Narita, Y.; Fukushima, S.; Tateishi, K.; Matsushita, Y.; Yoshida, A.; Miyakita, Y.; Ohno, M.; Collins, V.P.; Kawahara, N.; et al. Upregulating mutations in the tert promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss. Acta Neuropathol. 2013, 126, 267–276.
Nault, J.C.; Mallet, M.; Pilati, C.; Calderaro, J.; Bioulac-Sage, P.; Laurent, C.; Laurent, A.; Cherqui, D.; Balabaud, C.; Zucman-Rossi, J. High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions. Nat. Commun. 2013, 4, 2218.
Knight, J.C.; Renwick, P.J.; Dal Cin, P.; Van den Berghe, H.; Fletcher, C.D. Translocation t(12;16)(q13;p11) in myxoid liposarcoma and round cell liposarcoma: Molecular and cytogenetic analysis. Cancer Res. 1995, 55, 24–27.
Hummel, S.; VENTURA Ferreira, M.S.; Heudobler, D.; Huber, E.; Fahrenkamp, D.; Gremse, F.; Schmid, K.; Muller-Newen, G.; Ziegler, P.; Jost, E.; et al. Telomere shortening in enterocytes of patients with uncontrolled acute intestinal graft-versus-host disease. Blood 2015, 126, 2518–2521.
Ventura Ferreira, M.S.; Crysandt, M.; Ziegler, P.; Hummel, S.; Wilop, S.; Kirschner, M.; Schemionek, M.; Jost, E.; Wagner, W.; Brummendorf, T.H.; et al. Evidence for a pre-existing telomere deficit in non-clonal hematopoietic stem cells in patients with acute myeloid leukemia. Ann. Hematol. 2017, 96, 1457–1461.
Collado, M.; Blasco, M.A.; Serrano, M. Cellular senescence in cancer and aging. Cell 2007, 130, 223–233.
Deng, Y.; Chan, S.S.; Chang, S. Telomere dysfunction and tumour suppression: The senescence connection. Nat. Rev. Cancer 2008, 8, 450–458.
Mitchell, J.R.; Wood, E.; Collins, K. A telomerase component is defective in the human disease dyskeratosis congenita. Nature 1999, 402, 551–555.
Kabjorn Gustafsson, C.; Stahlberg, A.; Engtrom, K.; Danielsson, A.; Turesson, I.; Aman, P. Cell senescence in myxoid/round cell liposarcoma. Sarcoma 2014, 2014, 208786.
Rodriguez, R.; Rubio, R.; Menendez, P. Modeling sarcomagenesis using multipotent mesenchymal stem cells. Cell Res. 2012, 22, 62–77.
Xiao, W.; Mohseny, A.B.; Hogendoorn, P.C.; Cleton-Jansen, A.M. Mesenchymal stem cell transformation and sarcoma genesis. Clin. Sarcoma Res. 2013, 3, 10.
Scheel, C.; Schaefer, K.L.; Jauch, A.; Keller, M.; Wai, D.; Brinkschmidt, C.; van Valen, F.; Boecker, W.; Dockhorn-Dworniczak, B.; Poremba, C. Alternative lengthening of telomeres is associated with chromosomal instability in osteosarcomas. Oncogene 2001, 20, 3835–3844.
Huang, D.S.; Wang, Z.; He, X.J.; Diplas, B.H.; Yang, R.; Killela, P.J.; Meng, Q.; Ye, Z.Y.; Wang, W.; Jiang, X.T.; et al. Recurrent tert promoter mutations identified in a large-scale study of multiple tumour types are associated with increased tert expression and telomerase activation. Eur. J. Cancer 2015, 51, 969–976.
Borah, S.; Xi, L.; Zaug, A.J.; Powell, N.M.; Dancik, G.M.; Cohen, S.B.; Costello, J.C.; Theodorescu, D.; Cech, T.R. Cancer. Tert promoter mutations and telomerase reactivation in urothelial cancer. Science 2015, 347, 1006–1010.
Griewank, K.G.; Murali, R.; Puig-Butille, J.A.; Schilling, B.; Livingstone, E.; Potrony, M.; Carrera, C.; Schimming, T.; Moller, I.; Schwamborn, M.; et al. Tert promoter mutation status as an independent prognostic factor in cutaneous melanoma. J. Natl. Cancer Inst. 2014, 106, doi:10.1093/jnci/dju246.
Populo, H.; Boaventura, P.; Vinagre, J.; Batista, R.; Mendes, A.; Caldas, R.; Pardal, J.; Azevedo, F.; Honavar, M.; Guimaraes, I.; et al. Tert promoter mutations in skin cancer: The effects of sun exposure and x-irradiation. J. Investig. Dermatol. 2014, 134, 2251–2257.
Remke, M.; Ramaswamy, V.; Peacock, J.; Shih, D.J.; Koelsche, C.; Northcott, P.A.; Hill, N.; Cavalli, F.M.; Kool, M.; Wang, X.; et al. Tert promoter mutations are highly recurrent in shh subgroup medulloblastoma. Acta Neuropathol. 2013, 126, 917–929.
Rachakonda, P.S.; Hosen, I.; de Verdier, P.J.; Fallah, M.; Heidenreich, B.; Ryk, C.; Wiklund, N.P.; Steineck, G.; Schadendorf, D.; Hemminki, K.; et al. Tert promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism. Proc. Natl. Acad. Sci. USA 2013, 110, 17426–17431.
Wu, S.; Huang, P.; Li, C.; Huang, Y.; Li, X.; Wang, Y.; Chen, C.; Lv, Z.; Tang, A.; Sun, X.; et al. Telomerase reverse transcriptase gene promoter mutations help discern the origin of urogenital tumors: A genomic and molecular study. Eur. Urol. 2014, 65, 274–277.
Qu, Y.; Dang, S.; Wu, K.; Shao, Y.; Yang, Q.; Ji, M.; Shi, B.; Hou, P. Tert promoter mutations predict worse survival in laryngeal cancer patients. Int. J. Cancer 2014, 135, 1008–1010.
Melo, M.; da Rocha, A.G.; Vinagre, J.; Batista, R.; Peixoto, J.; Tavares, C.; Celestino, R.; Almeida, A.; Salgado, C.; Eloy, C.; et al. Tert promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J. Clin. Endocrinol. Metab. 2014, 99, E754–E765.
Liu, T.; Wang, N.; Cao, J.; Sofiadis, A.; Dinets, A.; Zedenius, J.; Larsson, C.; Xu, D. The age- and shorter telomere-dependent tert promoter mutation in follicular thyroid cell-derived carcinomas. Oncogene 2014, 33, 4978–4984.
George, J.R.; Henderson, Y.C.; Williams, M.D.; Roberts, D.B.; Hei, H.; Lai, S.Y.; Clayman, G.L. Association of tert promoter mutation, but not braf mutation, with increased mortality in ptc. J. Clin. Endocrinol. Metab. 2015, 100, E1550–E1559.
Gao, K.; Li, G.; Qu, Y.; Wang, M.; Cui, B.; Ji, M.; Shi, B.; Hou, P. Tert promoter mutations and long telomere length predict poor survival and radiotherapy resistance in gliomas. Oncotarget 2016, 7, 8712–8725.
Schneider, R.K.; Schenone, M.; Ferreira, M.V.; Kramann, R.; Joyce, C.E.; Hartigan, C.; Beier, F.; Brummendorf, T.H.; Germing, U.; Platzbecker, U.; et al. Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by s100a8 and s100a9. Nat. Med. 2016, 22, 288–297.
Werner, B.; Beier, F.; Hummel, S.; Balabanov, S.; Lassay, L.; Orlikowsky, T.; Dingli, D.; Brummendorf, T.H.; Traulsen, A. Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions. eLife 2015, 4, e08687.
Beier, F.; Masouleh, B.K.; Buesche, G.; Ventura Ferreira, M.S.; Schneider, R.K.; Ziegler, P.; Wilop, S.; Vankann, L.; Gattermann, N.; Platzbecker, U.; et al. Telomere dynamics in patients with del (5q) mds before and under treatment with lenalidomide. Leuk. Res. 2015, 39, 1292–1298.
Beier, F.; Foronda, M.; Martinez, P.; Blasco, M.A. Conditional trf1 knockout in the hematopoietic compartment leads to bone marrow failure and recapitulates clinical features of dyskeratosis congenita. Blood 2012, 120, 2990–3000.
Heaphy, C.M.; Subhawong, A.P.; Hong, S.M.; Goggins, M.G.; Montgomery, E.A.; Gabrielson, E.; Netto, G.J.; Epstein, J.I.; Lotan, T.L.; Westra, W.H.; et al. Prevalence of the alternative lengthening of telomeres telomere maintenance mechanism in human cancer subtypes. Am. J. Pathol. 2011, 179, 1608–1615.