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Variation at the TERT locus and predisposition for cancer

Published online by Cambridge University Press:  18 May 2010

Duncan M. Baird
Affiliation:
Department of Pathology, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK. E-mail: bairddm@cardiff.ac.uk
Corresponding
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Abstract

Telomerase and the control of telomere length are intimately linked to the process of tumourigenesis in humans. Here I review the evidence that variation at the 5p15.33 locus, which contains the TERT gene (encoding the catalytic subunit of telomerase), might play a role in the determination of cancer risk. Mutations in the coding regions of TERT can affect telomerase activity and telomere length, and create severe clinical phenotypes, including bone marrow failure syndromes and a substantive increase in cancer frequency. Variants within the TERT gene have been associated with increased risk of haematological malignancies, including myelodysplastic syndrome and acute myeloid leukaemia as well as chronic lymphocytic leukaemia. Furthermore, there is good evidence from a number of independent genome-wide association studies to implicate variants at the 5p15.33 locus in cancer risk at several different sites: lung cancer, basal cell carcinoma and pancreatic cancer show strong associations, while bladder, prostate and cervical cancer and glioma also show risk alleles in this region. Thus, multiple independent lines of evidence have implicated variation in the TERT gene as a risk factor for cancer. The mechanistic basis of these risk variants is yet to be established; however, the basic biology suggests that telomere length control is a tantalising candidate mechanism underlying cancer risk.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2010

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References

1Olovnikov, A.M. (1971) Principle of marginotomy in template synthesis of polynucleotides. Doklady Akademii Nauk SSSR 201, 1496-1499Google ScholarPubMed
2Greider, C.W. and Blackburn, E.H. (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405-413CrossRefGoogle ScholarPubMed
3Bodnar, A.G. et al. (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349-352CrossRefGoogle ScholarPubMed
4Engelhardt, M. et al. (1997) Relative contribution of normal and neoplastic cells determines telomerase activity and telomere length in primary cancers of the prostate, colon, and sarcoma. Clinical Cancer Research 3, 1849-1857Google ScholarPubMed
5Kolquist, K.A. et al. (1998) Expression of TERT in early premalignant lesions and a subset of cells in normal tissues. Nature Genetics 19, 182-186CrossRefGoogle Scholar
6Rooney, P.H. et al. (1999) Comparative genomic hybridization and chromosomal instability in solid tumours. British Journal of Cancer 80, 862-873CrossRefGoogle ScholarPubMed
7Cao, Y., Bryan, T.M. and Reddel, R.R. (2008) Increased copy number of the TERT and TERC telomerase subunit genes in cancer cells. Cancer Science 99, 1092-1099CrossRefGoogle ScholarPubMed
8Kang, J.U. et al. (2008) Gain at chromosomal region 5p15.33, containing TERT, is the most frequent genetic event in early stages of non-small cell lung cancer. Cancer Genetics and Cytogenetics 182, 1-11CrossRefGoogle ScholarPubMed
9Hwang, K.T. et al. (2008) Genomic copy number alterations as predictive markers of systemic recurrence in breast cancer. International Journal of Cancer 123, 1807-1815CrossRefGoogle ScholarPubMed
10Yamamoto, Y. et al. (2007) Gain of 5p15.33 is associated with progression of bladder cancer. Oncology 72, 132-138CrossRefGoogle ScholarPubMed
11Zienolddiny, S. et al. (2009) The TERT-CLPTM1L lung cancer susceptibility variant associates with higher DNA adduct formation in the lung. Carcinogenesis 30, 1368-1371CrossRefGoogle ScholarPubMed
12Yamamoto, K. et al. (2001) A novel gene, CRR9, which was up-regulated in CDDP-resistant ovarian tumor cell line, was associated with apoptosis. Biochemical and Biophysical Research Communications 280, 1148-1154CrossRefGoogle ScholarPubMed
13Takakura, M. et al. (2005) Function of AP-1 in transcription of the telomerase reverse transcriptase gene (TERT) in human and mouse cells. Molecular and Cellular Biology 25, 8037-8043CrossRefGoogle ScholarPubMed
14Yatabe, N. et al. (2004) HIF-1-mediated activation of telomerase in cervical cancer cells. Oncogene 23, 3708-3715CrossRefGoogle ScholarPubMed
15Kyo, S. et al. (2000) Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT). Nucleic Acids Research 28, 669-677CrossRefGoogle Scholar
16Kyo, S. et al. (1999) Estrogen activates telomerase. Cancer Research 59, 5917-5921Google ScholarPubMed
17Calado, R.T. et al. (2009) Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells. Blood 114, 2236-2243CrossRefGoogle ScholarPubMed
18Kanaya, T. et al. (2000) Adenoviral expression of p53 represses telomerase activity through down-regulation of human telomerase reverse transcriptase transcription. Clinical Cancer Research 6, 1239-1247Google ScholarPubMed
19Oh, S. et al. (1999) The Wilms' tumor 1 tumor suppressor gene represses transcription of the human telomerase reverse transcriptase gene. Journal of Biological Chemistry 274, 37473-37478CrossRefGoogle ScholarPubMed
20Fujimoto, K. et al. (2000) Identification and characterization of negative regulatory elements of the human telomerase catalytic subunit (hTERT) gene promoter: possible role of MZF-2 in transcriptional repression of hTERT. Nucleic Acids Research 28, 2557-2562CrossRefGoogle ScholarPubMed
21Kyo, S. et al. (2008) Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers. Cancer Science 99, 1528-1538CrossRefGoogle ScholarPubMed
22de Lange, T. (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes and Development 19, 2100-2110CrossRefGoogle ScholarPubMed
23Mitchell, J.R., Wood, E. and Collins, K. (1999) A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402, 551-555Google ScholarPubMed
24Mochizuki, Y. et al. (2004) Mouse dyskerin mutations affect accumulation of telomerase RNA and small nucleolar RNA, telomerase activity, and ribosomal RNA processing. Proceedings of the National Academy of Sciences of the United States of America 101, 10756-10761CrossRefGoogle ScholarPubMed
25Fu, D. and Collins, K. (2003) Distinct biogenesis pathways for human telomerase RNA and H/ACA small nucleolar RNAs. Molecular Cell 11, 1361-1372CrossRefGoogle ScholarPubMed
26Pogacic, V., Dragon, F. and Filipowicz, W. (2000) Human H/ACA small nucleolar RNPs and telomerase share evolutionarily conserved proteins NHP2 and NOP10. Molecular and Cellular Biology 20, 9028-9040CrossRefGoogle Scholar
27Venteicher, A.S. et al. (2009) A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. Science 323, 644-648CrossRefGoogle ScholarPubMed
28Harley, C.B., Futcher, A.B. and Greider, C.W. (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345, 458-460CrossRefGoogle ScholarPubMed
29Levy, M.Z. et al. (1992) Telomere end-replication problem and cell aging. Journal of Molecular Biology 225, 951-960CrossRefGoogle ScholarPubMed
30Baird, D.M. et al. (2003) Extensive allelic variation and ultrashort telomeres in senescent human cells. Nature Genetics 33, 203-207CrossRefGoogle ScholarPubMed
31Weng, N.P. et al. (1995) Human naive and memory T lymphocytes differ in telomeric length and replicative potential. Proceedings of the National Academy of Sciences of the United States of America 92, 11091-11094CrossRefGoogle ScholarPubMed
32Capper, R. et al. (2007) The nature of telomere fusion and a definition of the critical telomere length in human cells. Genes and Development 21, 2495-2508CrossRefGoogle Scholar
33Baird, D.M. (2008) Mechanisms of telomeric instability. Cytogenetic and Genome Research 122, 308-314CrossRefGoogle ScholarPubMed
34Lansdorp, P.M. (2005) Major cutbacks at chromosome ends. Trends in Biochemical Sciences 30, 388-395CrossRefGoogle ScholarPubMed
35Cristofari, G. and Lingner, J. (2006) Telomere length homeostasis requires that telomerase levels are limiting. EMBO Journal 25, 565-574CrossRefGoogle ScholarPubMed
36Teixeira, M.T. et al. (2004) Telomere length homeostasis is achieved via a switch between telomerase- extendible and -nonextendible states. Cell 117, 323-335CrossRefGoogle Scholar
37Britt-Compton, B. et al. (2009) Short telomeres are preferentially elongated by telomerase in human cells. FEBS Letters 583, 3076-3080CrossRefGoogle ScholarPubMed
38Hathcock, K.S. et al. (2002) Haploinsufficiency of mTR results in defects in telomere elongation. Proceedings of the National Academy of Sciences of the United States of America 99, 3591-3596CrossRefGoogle ScholarPubMed
39Erdmann, N., Liu, Y. and Harrington, L. (2004) Distinct dosage requirements for the maintenance of long and short telomeres in mTert heterozygous mice. Proceedings of the National Academy of Sciences of the United States of America 101, 6080-6085CrossRefGoogle ScholarPubMed
40Nakamura, K. et al. (2002) Comparative analysis of telomere lengths and erosion with age in human epidermis and lingual epithelium. Journal of Investigative Dermatology 119, 1014-1019CrossRefGoogle ScholarPubMed
41Aida, J. et al. (2008) Basal cells have longest telomeres measured by tissue Q-FISH method in lingual epithelium. Experimental Gerontology 43, 833-839CrossRefGoogle ScholarPubMed
42Takubo, K. et al. (2002) Telomere lengths are characteristic in each human individual. Experimental Gerontology 37, 523-531CrossRefGoogle ScholarPubMed
43Yui, J., Chiu, C.P. and Lansdorp, P.M. (1998) Telomerase activity in candidate stem cells from fetal liver and adult bone marrow. Blood 91, 3255-3262Google ScholarPubMed
44Morrison, S.J. et al. (1996) Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity 5, 207-216CrossRefGoogle ScholarPubMed
45Broccoli, D., Young, J.W. and de Lange, T. (1995) Telomerase activity in normal and malignant hematopoietic cells. Proceedings of the National Academy of Sciences of the United States of America 92, 9082-9086CrossRefGoogle ScholarPubMed
46Chiu, C.P. et al. (1996) Differential expression of telomerase activity in hematopoietic progenitors from adult human bone marrow. Stem Cells 14, 239-248CrossRefGoogle ScholarPubMed
47Vaziri, H. et al. (1994) Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proceedings of the National Academy of Sciences of the United States of America 91, 9857-9860CrossRefGoogle ScholarPubMed
48Norrback, K.F. et al. (2001) Telomerase regulation and telomere dynamics in germinal centers. European Journal of Haematology 67, 309-317CrossRefGoogle ScholarPubMed
49Norrback, K.F. et al. (1996) Telomerase activation in normal B lymphocytes and non-Hodgkin's lymphomas. Blood 88, 222-229Google ScholarPubMed
50Hiyama, K. et al. (1995) Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. Journal of Immunology 155, 3711-3715Google ScholarPubMed
51Maini, M.K. et al. (1999) Virus-induced CD8+ T cell clonal expansion is associated with telomerase up-regulation and telomere length preservation: a mechanism for rescue from replicative senescence. Journal of Immunology 162, 4521-4526Google ScholarPubMed
52Hodes, R.J., Hathcock, K.S. and Weng, N.P. (2002) Telomeres in T and B cells. Nature Reviews Immunology 2, 699-706CrossRefGoogle ScholarPubMed
53Rufer, N. et al. (1999) Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood. Journal of Experimental Medicine 190, 157-167CrossRefGoogle Scholar
54Weng, N.P., Granger, L. and Hodes, R.J. (1997) Telomere lengthening and telomerase activation during human B cell differentiation. Proceedings of the National Academy of Sciences of the United States of America 94, 10827-10832CrossRefGoogle ScholarPubMed
55Hathcock, K.S. et al. (2003) Induction of telomerase activity and maintenance of telomere length in virus-specific effector and memory CD8+ T cells. Journal of Immunology 170, 147-152CrossRefGoogle ScholarPubMed
56Plunkett, F.J. et al. (2001) The flow cytometric analysis of telomere length in antigen-specific CD8+ T cells during acute Epstein-Barr virus infection. Blood 97, 700-707CrossRefGoogle ScholarPubMed
57Akbar, A.N., Beverley, P.C. and Salmon, M. (2004) Will telomere erosion lead to a loss of T-cell memory? Nature Reviews Immunology 4, 737-743CrossRefGoogle ScholarPubMed
58Nakamura, K.I. et al. (2007) Telomeric DNA length in cerebral gray and white matter is associated with longevity in individuals aged 70 years or older. Experimental Gerontology 42, 944-950CrossRefGoogle ScholarPubMed
59Benetos, A. et al. (2004) Short telomeres are associated with increased carotid atherosclerosis in hypertensive subjects. Hypertension 43, 182-185CrossRefGoogle ScholarPubMed
60Samani, N.J. et al. (2001) Telomere shortening in atherosclerosis. Lancet 358, 472-473CrossRefGoogle ScholarPubMed
61Valdes, A.M. et al. (2007) Telomere length in leukocytes correlates with bone mineral density and is shorter in women with osteoporosis. Osteoporosis International 18, 1203-1210CrossRefGoogle ScholarPubMed
62Epel, E.S. et al. (2004) Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences of the United States of America 101, 17312-17315CrossRefGoogle ScholarPubMed
63Valdes, A.M. et al. (2005) Obesity, cigarette smoking, and telomere length in women. Lancet 366, 662-664CrossRefGoogle ScholarPubMed
64Svenson, U., Ljungberg, B. and Roos, G. (2009) Telomere length in peripheral blood predicts survival in clear cell renal cell carcinoma. Cancer Research 69, 2896-2901CrossRefGoogle ScholarPubMed
65McGrath, M. et al. (2007) Telomere length, cigarette smoking, and bladder cancer risk in men and women. Cancer Epidemiology Biomarkers and Prevention 16, 815-819CrossRefGoogle ScholarPubMed
66Wu, X. et al. (2003) Telomere dysfunction: a potential cancer predisposition factor. Journal of the National Cancer Institute 95, 1211-1218CrossRefGoogle ScholarPubMed
67Widmann, T.A. et al. (2007) Short telomeres in aggressive non-Hodgkin's lymphoma as a risk factor in lymphomagenesis. Experimental Hematology 35, 939-946CrossRefGoogle ScholarPubMed
68Risques, R.A. et al. (2007) Leukocyte telomere length predicts cancer risk in Barrett's esophagus. Cancer Epidemiology Biomarkers and Prevention 16, 2649-2655CrossRefGoogle ScholarPubMed
69Svenson, U. et al. (2008) Breast cancer survival is associated with telomere length in peripheral blood cells. Cancer Research 68, 3618-3623CrossRefGoogle ScholarPubMed
70Shen, J. et al. (2007) Short telomere length and breast cancer risk: a study in sister sets. Cancer Research 67, 5538-5544CrossRefGoogle ScholarPubMed
71Bataille, V. et al. (2007) Nevus size and number are associated with telomere length and represent potential markers of a decreased senescence in vivo. Cancer Epidemiology Biomarkers and Prevention 16, 1499-1502CrossRefGoogle ScholarPubMed
72Han, J. et al. (2009) A prospective study of telomere length and the risk of skin cancer. Journal of Investigative Dermatology 129, 415-421CrossRefGoogle ScholarPubMed
73Sviderskaya, E.V. et al. (2003) p16/cyclin-dependent kinase inhibitor 2A deficiency in human melanocyte senescence, apoptosis, and immortalization: possible implications for melanoma progression. Journal of the National Cancer Institute 95, 723-732CrossRefGoogle ScholarPubMed
74Martin-Ruiz, C.M. et al. (2005) Telomere length in white blood cells is not associated with morbidity or mortality in the oldest old: a population-based study. Aging Cell 4, 287-290CrossRefGoogle ScholarPubMed
75Nordfjall, K. et al. (2009) The individual blood cell telomere attrition rate is telomere length dependent. PLoS Genetics 5, e1000375CrossRefGoogle ScholarPubMed
76Aviv, A. (2008) The epidemiology of human telomeres: faults and promises. Journals of Gerontology Series A Biological Sciences and Medical Sciences 63, 979-983CrossRefGoogle ScholarPubMed
77Baird, D.M. (2008) Telomere dynamics in human cells. Biochimie 90, 116-121CrossRefGoogle ScholarPubMed
78Britt-Compton, B. et al. (2009) Telomere dynamics during replicative senescence are not directly modulated by conditions of oxidative stress in IMR90 fibroblast cells. BiogerontologyCrossRefGoogle ScholarPubMed
79von Zglinicki, T. (2002) Oxidative stress shortens telomeres. Trends in Biochemical Sciences 27, 339-344CrossRefGoogle ScholarPubMed
80von Zglinicki, T. et al. (1995) Mild hyperoxia shortens telomeres and inhibits proliferation of fibroblasts: a model for senescence? Experimental Cell Research 220, 186-193CrossRefGoogle ScholarPubMed
81Okuda, K. et al. (2002) Telomere length in the newborn. Pediatric Research 52, 377-381CrossRefGoogle ScholarPubMed
82Youngren, K. et al. (1998) Synchrony in telomere length of the human fetus. Human Genetics 102, 640-643CrossRefGoogle ScholarPubMed
83Baird, D.M. et al. (2006) Telomere instability in the male germline. Human Molecular Genetics 15, 45-51CrossRefGoogle ScholarPubMed
84Andrew, T. et al. (2006) Mapping genetic loci that determine leukocyte telomere length in a large sample of unselected female sibling pairs. American Journal of Human Genetics 78, 480-486CrossRefGoogle Scholar
85Slagboom, P.E., Droog, S. and Boomsma, D.I. (1994) Genetic determination of telomere size in humans: a twin study of three age groups. American Journal of Human Genetics 55, 876-882Google ScholarPubMed
86Vasa-Nicotera, M. et al. (2005) Mapping of a major locus that determines telomere length in humans. American Journal of Human Genetics 76, 147-151CrossRefGoogle Scholar
87Mangino, M. et al. (2009) A genome-wide association study identifies a novel locus on chromosome 18q12.2 influencing white cell telomere length. Journal of Medical Genetics 46, 451-454CrossRefGoogle ScholarPubMed
88d'Adda di Fagagna, F. et al. (2003) A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194-198CrossRefGoogle ScholarPubMed
89Jeyapalan, J.C. et al. (2007) Accumulation of senescent cells in mitotic tissue of aging primates. Mechanisms of Ageing and Development 128, 36-44CrossRefGoogle ScholarPubMed
90Herbig, U. et al. (2006) Cellular senescence in aging primates. Science 311, 1257CrossRefGoogle ScholarPubMed
91Campisi, J. (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120, 513-522CrossRefGoogle ScholarPubMed
92Krtolica, A. et al. (2001) Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proceedings of the National Academy of Sciences of the United States of America 98, 12072-12077CrossRefGoogle ScholarPubMed
93Blasco, M.A. et al. (1997) Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25-34CrossRefGoogle ScholarPubMed
94Herrera, E. et al. (1999) Disease states associated with telomerase deficiency appear earlier in mice with short telomeres. EMBO Journal 18, 2950-2960CrossRefGoogle ScholarPubMed
95Lee, H.W. et al. (1998) Essential role of mouse telomerase in highly proliferative organs. Nature 392, 569-574Google ScholarPubMed
96Rudolph, K.L. et al. (1999) Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96, 701-712CrossRefGoogle ScholarPubMed
97Chin, L. et al. (1999) p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97, 527-538CrossRefGoogle ScholarPubMed
98Counter, C.M. et al. (1992) Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO Journal 11, 1921-1929Google ScholarPubMed
99Shay, J.W. et al. (1993) E6 of human papillomavirus type 16 can overcome the M1 stage of immortalization in human mammary epithelial cells but not in human fibroblasts. Oncogene 8, 1407-1413Google ScholarPubMed
100Letsolo, B.T., Rowson, J. and Baird, D.M. (2010) Fusion of short telomeres in human cells is characterised by extensive deletion and microhomology and can result in complex rearrangements. Nucleic Acids Research 38, 1841-1852CrossRefGoogle Scholar
101Murnane, J.P. and Sabatier, L. (2004) Chromosome rearrangements resulting from telomere dysfunction and their role in cancer. Bioessays 26, 1164-1174CrossRefGoogle Scholar
102Artandi, S.E. et al. (2000) Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature 406, 641-645CrossRefGoogle ScholarPubMed
103Mitelman, F. et al. (1997) Clinical significance of cytogenetic findings in solid tumors. Cancer Genetics and Cytogenetics 95, 1-8CrossRefGoogle ScholarPubMed
104Shih, I.M. et al. (2001) Evidence that genetic instability occurs at an early stage of colorectal tumorigenesis. Cancer Research 61, 818-822Google ScholarPubMed
105Engelhardt, M. et al. (1997) Telomerase and telomere length in the development and progression of premalignant lesions to colorectal cancer. Clinical Cancer Research 3, 1931-1941Google ScholarPubMed
106Hastie, N.D. et al. (1990) Telomere reduction in human colorectal carcinoma and with ageing. Nature 346, 866-868CrossRefGoogle ScholarPubMed
107Meeker, A.K. et al. (2002) Telomere shortening is an early somatic DNA alteration in human prostate tumorigenesis. Cancer Research 62, 6405-6409Google ScholarPubMed
108Chin, K. et al. (2004) In situ analyses of genome instability in breast cancer. Nature Genetics 36, 984-988CrossRefGoogle ScholarPubMed
109Rudolph, K.L. et al. (2001) Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nature Genetics 28, 155-159CrossRefGoogle ScholarPubMed
110Gordon, K.E. et al. (2003) High levels of telomere dysfunction bestow a selective disadvantage during the progression of human oral squamous cell carcinoma. Cancer Research 63, 458-467Google ScholarPubMed
111Gisselsson, D. et al. (2001) Telomere dysfunction triggers extensive DNA fragmentation and evolution of complex chromosome abnormalities in human malignant tumors. Proceedings of the National Academy of Sciences of the United States of America 98, 12683-12688CrossRefGoogle ScholarPubMed
112Nakamura, T.M. et al. (1997) Telomerase catalytic subunit homologs from fission yeast and human. Science 277, 955-959CrossRefGoogle ScholarPubMed
113Savage, S.A. et al. (2005) Genetic variation, nucleotide diversity, and linkage disequilibrium in seven telomere stability genes suggest that these genes may be under constraint. Human Mutation 26, 343-350CrossRefGoogle ScholarPubMed
114Kirwan, M. and Dokal, I. (2009) Dyskeratosis congenita, stem cells and telomeres. Biochimica et Biophysica Acta 1792, 371-379CrossRefGoogle ScholarPubMed
115Armanios, M. et al. (2005) Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. Proceedings of the National Academy of Sciences of the United States of America 102, 15960-15964CrossRefGoogle ScholarPubMed
116Goldman, F. et al. (2005) The effect of TERC haploinsufficiency on the inheritance of telomere length. Proceedings of the National Academy of Sciences of the United States of America 102, 17119-17124CrossRefGoogle ScholarPubMed
117Vulliamy, T. et al. (2004) Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. Nature Genetics 36, 447-449CrossRefGoogle ScholarPubMed
118Kirwan, M. et al. (2008) Circulating haematopoietic progenitors are differentially reduced amongst subtypes of dyskeratosis congenita. British Journal of Haematology 140, 719-722CrossRefGoogle ScholarPubMed
119Marley, S.B. et al. (1999) Evidence for a continuous decline in haemopoietic cell function from birth: application to evaluating bone marrow failure in children. British Journal of Haematology 106, 162-166CrossRefGoogle ScholarPubMed
120Dokal, I. and Luzzatto, L. (1994) Dyskeratosis congenita is a chromosomal instability disorder. Leukemia and Lymphoma 15, 1-7CrossRefGoogle ScholarPubMed
121Dokal, I. and Vulliamy, T. (2008) Inherited aplastic anaemias/bone marrow failure syndromes. Blood Reviews 22, 141-153CrossRefGoogle ScholarPubMed
122Feinberg, A.P. and Coffey, D.S. (1982) Organ site specificity for cancer in chromosomal instability disorders. Cancer Research 42, 3252-3254Google ScholarPubMed
123Alter, B.P. et al. (2009) Cancer in dyskeratosis congenita. Blood 113, 6549-6557CrossRefGoogle ScholarPubMed
124Marsh, J.C. et al. (1992) “Stem cell” origin of the hematopoietic defect in dyskeratosis congenita. Blood 79, 3138-3144Google ScholarPubMed
125Goldman, F.D. et al. (2008) Characterization of primitive hematopoietic cells from patients with dyskeratosis congenita. Blood 111, 4523-4531CrossRefGoogle ScholarPubMed
126Kirwan, M. and Dokal, I. (2009) Dyskeratosis congenita, stem cells and telomeres. Biochimica et Biophysica Acta 1792, 371-379CrossRefGoogle ScholarPubMed
127Ball, S.E. et al. (1998) Progressive telomere shortening in aplastic anemia. Blood 91, 3582-3592Google ScholarPubMed
128Thornley, I. et al. (2002) Abnormal telomere shortening in leucocytes of children with Shwachman-Diamond syndrome. British Journal of Haematology 117, 189-192CrossRefGoogle ScholarPubMed
129Yamaguchi, H. et al. (2005) Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. New England Journal of Medicine 352, 1413-1424CrossRefGoogle ScholarPubMed
130Lipton, J.M. et al. (2006) Improving clinical care and elucidating the pathophysiology of Diamond Blackfan anemia: an update from the Diamond Blackfan Anemia Registry. Pediatric Blood and Cancer 46, 558-564CrossRefGoogle ScholarPubMed
131Alter, B.P. (2007) Diagnosis, genetics, and management of inherited bone marrow failure syndromes. Hematology/American Society of Hematology Education Program 29-39Google ScholarPubMed
132Socie, G. et al. (1993) Malignant tumors occurring after treatment of aplastic anemia. European Bone Marrow Transplantation-Severe Aplastic Anaemia Working Party. New England Journal of Medicine 329, 1152-1157CrossRefGoogle ScholarPubMed
133Dokal, I. et al. (1992) Dyskeratosis congenita fibroblasts are abnormal and have unbalanced chromosomal rearrangements. Blood 80, 3090-3096Google ScholarPubMed
134Yamaguchi, H. et al. (2003) Mutations of the human telomerase RNA gene (TERC) in aplastic anemia and myelodysplastic syndrome. Blood 102, 916-918CrossRefGoogle ScholarPubMed
135Calado, R.T. et al. (2009) Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia. Proceedings of the National Academy of Sciences of the United States of America 106, 1187-1192CrossRefGoogle ScholarPubMed
136Kirwan, M. et al. (2009) Defining the pathogenic role of telomerase mutations in myelodysplastic syndrome and acute myeloid leukemia. Human Mutation 30, 1567-1573CrossRefGoogle ScholarPubMed
137Hills, M. and Lansdorp, P.M. (2009) Short telomeres resulting from heritable mutations in the telomerase reverse transcriptase gene predispose for a variety of malignancies. Annals of the New York Academy of Sciences 1176, 178-190CrossRefGoogle ScholarPubMed
138Smith, M.L. et al. (2004) Mutation of CEBPA in familial acute myeloid leukemia. New England Journal of Medicine 351, 2403-2407CrossRefGoogle ScholarPubMed
139Song, W.J. et al. (1999) Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nature Genetics 23, 166-175Google ScholarPubMed
140Saccone, S.F. et al. (2007) Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Human Molecular Genetics 16, 36-49CrossRefGoogle Scholar
141Hung, R.J. et al. (2008) A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature 452, 633-637CrossRefGoogle ScholarPubMed
142Amos, C.I. et al. (2008) Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nature Genetics 40, 616-622CrossRefGoogle ScholarPubMed
143Thorgeirsson, T.E. et al. (2008) A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 452, 638-642CrossRefGoogle ScholarPubMed
144McKay, J.D. et al. (2008) Lung cancer susceptibility locus at 5p15.33. Nature Genetics 40, 1404-1406CrossRefGoogle ScholarPubMed
145Wang, Y. et al. (2008) Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nature Genetics 40, 1407-1409CrossRefGoogle ScholarPubMed
146Wang, Y. et al. (2010) Role of 5p15.33 (TERT-CLPTM1L), 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) variation and lung cancer risk in never smokers. Carcinogenesis 31, 234-238CrossRefGoogle ScholarPubMed
147Landi, M.T. et al. (2009) A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. American Journal of Human Genetics 85, 679-691CrossRefGoogle ScholarPubMed
148Broderick, P. et al. (2009) Deciphering the impact of common genetic variation on lung cancer risk: a genome-wide association study. Cancer Research 69, 6633-6641CrossRefGoogle ScholarPubMed
149Rafnar, T. et al. (2009) Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nature Genetics 41, 221-227CrossRefGoogle ScholarPubMed
150Choi, J.E. et al. (2009) Polymorphisms in telomere maintenance genes and risk of lung cancer. Cancer Epidemiology Biomarkers and Prevention 18, 2773-2781CrossRefGoogle ScholarPubMed
151Hsu, C.P. et al. (2006) Ets2 binding site single nucleotide polymorphism at the hTERT gene promoter–effect on telomerase expression and telomere length maintenance in non-small cell lung cancer. European Journal of Cancer 42, 1466-1474CrossRefGoogle ScholarPubMed
152Dwyer, J.M. and Liu, J.P. (2010) Ets2 transcription factor, telomerase activity and breast cancer. Clinical and Experimental Pharmacology and Physiology 37, 83-87CrossRefGoogle ScholarPubMed
153Park, J. et al. (2001) Lung cancer in patients with idiopathic pulmonary fibrosis. European Respiratory Journal 17, 1216-1219CrossRefGoogle ScholarPubMed
154Armanios, M.Y. et al. (2007) Telomerase mutations in families with idiopathic pulmonary fibrosis. New England Journal of Medicine 356, 1317-1326CrossRefGoogle ScholarPubMed
155Tsakiri, K.D. et al. (2007) Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proceedings of the National Academy of Sciences of the United States of America 104, 7552-7557CrossRefGoogle ScholarPubMed
156Mushiroda, T. et al. (2008) A genome-wide association study identifies an association of a common variant in TERT with susceptibility to idiopathic pulmonary fibrosis. Journal of Medical Genetics 45, 654-656CrossRefGoogle ScholarPubMed
157Leem, S.H. et al. (2002) The human telomerase gene: complete genomic sequence and analysis of tandem repeat polymorphisms in intronic regions. Oncogene 21, 769-777CrossRefGoogle ScholarPubMed
158Wang, L. et al. (2003) Association of a functional tandem repeats in the downstream of human telomerase gene and lung cancer. Oncogene 22, 7123-7129CrossRefGoogle ScholarPubMed
159Stacey, S.N. et al. (2009) New common variants affecting susceptibility to basal cell carcinoma. Nature Genetics 41, 909-914CrossRefGoogle ScholarPubMed
160Shete, S. et al. (2009) Genome-wide association study identifies five susceptibility loci for glioma. Nature Genetics 41, 899-904CrossRefGoogle ScholarPubMed
161Wager, M. et al. (2008) Prognostic molecular markers with no impact on decision-making: the paradox of gliomas based on a prospective study. British Journal of Cancer 98, 1830-1838CrossRefGoogle ScholarPubMed
162Wang, L. et al. (2006) Survival prediction in patients with glioblastoma multiforme by human telomerase genetic variation. Journal of Clinical Oncology 24, 1627-1632CrossRefGoogle ScholarPubMed
163Carpentier, C. et al. (2007) Association of telomerase gene hTERT polymorphism and malignant gliomas. Journal of Neuro-Oncology 84, 249-253CrossRefGoogle ScholarPubMed
164Andersson, U. et al. (2009) MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and to glioblastoma outcome. International Journal of Cancer 125, 968-972CrossRefGoogle ScholarPubMed
165Fordyce, C.A. et al. (2006) Telomere content correlates with stage and prognosis in breast cancer. Breast Cancer Research and Treatment 99, 193-202CrossRefGoogle ScholarPubMed
166Savage, S.A. et al. (2007) Genetic variation in five genes important in telomere biology and risk for breast cancer. British Journal of Cancer 97, 832-836CrossRefGoogle ScholarPubMed
167Varadi, V. et al. (2009) A functional promoter polymorphism in the TERT gene does not affect inherited susceptibility to breast cancer. Cancer Genetics and Cytogenetics 190, 71-74CrossRefGoogle Scholar
168Gertler, R. et al. (2004) Telomere length and human telomerase reverse transcriptase expression as markers for progression and prognosis of colorectal carcinoma. Journal of Clinical Oncology 22, 1807-1814CrossRefGoogle ScholarPubMed
169Gertler, R. et al. (2002) Prognostic potential of the telomerase subunit human telomerase reverse transcriptase in tumor tissue and nontumorous mucosa from patients with colorectal carcinoma. Cancer 95, 2103-2111CrossRefGoogle ScholarPubMed
170Tomlinson, I.P. et al. (2008) A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3. Nature Genetics 40, 623-630CrossRefGoogle ScholarPubMed
171Tenesa, A. et al. (2008) Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nature Genetics 40, 631-637CrossRefGoogle ScholarPubMed
172Petersen, G.M. et al. (2010) A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nature Genetics 42, 224-228CrossRefGoogle ScholarPubMed
173Bryan, T.M. et al. (1995) Telomere elongation in immortal human cells without detectable telomerase activity. EMBO Journal 14, 4240-4248Google ScholarPubMed
174Fauce, S.R. et al. (2008) Telomerase-based pharmacologic enhancement of antiviral function of human CD8+ T lymphocytes. Journal of Immunology 181, 7400-7406CrossRefGoogle ScholarPubMed
Titia de Lange, T., Lundblad, V. and Blackburn, E., eds (2006) Telomeres, Second Edition, Cold Spring Harbor Press, New YorkGoogle Scholar

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