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

Volumn 1176, Issue , 2009, Pages 178-190

  Hills, Mark ^a   Lansdorp, Peter M ^a,b  

^a BRITISH COLUMBIA CANCER AGENCY   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

AML; Cancer predisposition; Hematopoietic hierarchy; Heritable mutations; HTERT; Mutator phenotype; Telomerase; Telomere length

Indexed keywords

TELOMERASE REVERSE TRANSCRIPTASE;

ACUTE GRANULOCYTIC LEUKEMIA; B CELL LYMPHOMA; CANCER SUSCEPTIBILITY; CELL AGING; CHRONIC LYMPHATIC LEUKEMIA; CONFERENCE PAPER; CONTROLLED STUDY; DNA REPAIR; GENE; GENE MUTATION; GENETIC SUSCEPTIBILITY; GENOMIC INSTABILITY; HERITABILITY; HTERT GENE; HUMAN; HUMAN CELL; MULTIPLE MYELOMA; MUTATION RATE; POLYMERASE CHAIN REACTION; TELOMERE;

EID: 70349815091     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.2009.04565.x     Document Type: Conference Paper

References (64)

1. Moyzis, R.K. et al. 1988. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc. Natl. Acad. Sci. USA 85: 6622-6626.
2. Makarov, V.L., Y. Hirose & J.P. Langmore. 1997. Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telom-ere shortening. Cell 88: 657-666.
3. Griffith, J.D. et al. 1999. Mammalian telomeres end in a large duplex loop. Cell 97: 503-514.
4. Olovnikov, A.M. 1973. A theory of marginotomy. The incomplete copying of template margin in en-zymic synthesis of polynucleotides and biological sig-nificance of the phenomenon. J. Theor. Biol. 41: 181-190.
5. Huffman, K.E. et al. 2000. Telomere shortening is proportional to the size of the G-rich telomeric 3'-overhang. J. Biol. Chem. 275: 19719-19722.
6. Harley, C.B. et al. 1992. The telomere hypothesis of cellular aging. Exp. Gerontol. 27: 375-382.
7. Hayflick, L. 1965. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 37: 614-636.
8. Blackburn, E.H. 2001. Switching and signaling at the telomere. Cell 106: 661-673.
9. Feng, J. et al. 1995. The RNA component of human telomerase. Science 269: 1236-1241.
10. Morin, G.B. 1989. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell 59: 521-529.
11. Cohen, S.B. et al. 2007. Protein composition of catalytically active human telomerase from immortal cells. Science 315: 1850-1853.
12. Counter, C.M. et al. 1995. Telomerase activity in normal leukocytes and in hematologic malignancies. Blood 85: 2315-2320.
13. Vaziri, H. et al. 1994. Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc. Natl. Acad. Sci. USA 91: 9857-9860.
14. Rufer, 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. J. Exp. Med. 190: 157-167.
15. Ouyang, Q. et al. 2007. Telomere length in human natural killer cell subsets. Ann. N. Y. Acad. Sci. 1106: 240-252.
16. Van Ziffle, J.A., G.M. Baerlocher & P.M. Lansdorp. 2003. Telomere length in subpopulations of human hematopoietic cells. Stem Cells 21: 654-660.
17. Baird, D.M. et al. 2003. Extensive allelic variation and ultrashort telomeres in senescent human cells. Nat. Genet. 33: 203-207.
18. Hills, M. et al. 2009. Probing the mitotic history and developmental stage of hematopoietic cells using Single Telomere Length Analysis (STELA). Blood, in press.
19. Martens, U.M. et al. 2002. Telomere maintenance in human B lymphocytes. Br. J. Haematol. 119: 810-818.
20. Weng, N.P., L. Granger & R.J. Hodes. 1997. Telom-ere lengthening and telomerase activation during human B cell differentiation. Proc. Natl. Acad. Sci. USA 94: 10827-10832.
21. Lewis, N.L. et al. 2004. Measurable immune dysfunction and telomere attrition in long-term allogeneic transplant recipients. Bone Marrow Transplant. 33: 71-78.
22. Awaya, N. et al. 2002. Telomere shortening in hematopoietic stem cell transplantation: a potential mechanism for late graft failure? Biol. Blood Marrow Transplant. 8: 597-600.
23. Rufer, N. et al. 2001. Accelerated telomere shortening in hematological lineages is limited to the first year following stem cell transplantation. Blood 97: 575-577.
24. Pipes, B.L. et al. 2006. Telomere length changes after umbilical cord blood transplant. Transfusion 46: 1038-1043.
25. Vulliamy, T.J. & I. Dokal. 2008. Dyskeratosis con-genita: the diverse clinical presentation of mutations in the telomerase complex. Biochimie 90: 122-130.
26. Aubert, G. & P.M. Lansdorp. 2008. Telomeres and aging. Physiol. Rev. 88: 557-579.
27. Mitchell, J.R., E. Wood & K. Collins. 1999. A telomerase component is defective in the human disease dyskeratosis congenita. Nature 402: 551-555.
28. Wong, J.M. & K. Collins. 2006. Telomerase RNA level limits telomere maintenance in X-linked dysker-atosis congenita. Genes Dev. 20: 2848-2858.
29. Ly, H. et al. 2005. Identification and functional characterization of 2 variant alleles of the telomerase RNA template gene (TERC) in a patient with dysker-atosis congenita. Blood 106: 1246-1252.
30. Savage, S.A. et al. 2006. Mutations in the reverse transcriptase component of telomerase (TERT) in patients with bone marrow failure. Blood Cells Mol. Dis. 37: 134-136.
31. Vulliamy, T. et al. 2001. The RNA component of telomerase is mutated in autosomal dominant dysker-atosis congenita. Nature 413: 432-435. (Pubitemid 32928599)
32. Yamaguchi, H. et al. 2005. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N. Engl. J. Med. 352: 1413-1424.
33. Yamaguchi, H. et al. 2003. Mutations of the human telomerase RNA gene (TERC) in aplastic anemia and myelodysplastic syndrome. Blood 102: 916-918.
34. Armanios, M.Y. et al. 2007. Telomerase mutations in families with idiopathic pulmonary fibrosis. N. Engl. J. Med. 356: 1317-1326.
35. Savage, S.A. et al. 2008. TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. Am. J. Hum. Genet. 82: 501-509.
36. Vulliamy, T. et al. 2008. Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita. Proc. Natl. Acad. Sci. USA 105: 8073-8078.
37. Walne, A.J. et al. 2007. Genetic heterogeneity in auto-somal recessive dyskeratosis congenita with one subtype due to mutations in the telomerase-associated protein NOP10. Hum. Mol. Genet. 16: 1619-1629.
38. Ly, H. et al. 2005. Functional characterization of telomerase RNA variants found in patients with hematologic disorders. Blood 105: 2332-2339.
39. Calado, R.T. et al. 2009. Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia. Proc. Natl. Acad. Sci. USA. 106: 1187-1192.
40. Xin, Z.T. et al. 2007. Functional characterization of natural telomerase mutations found in patients with hematologic disorders. Blood 109: 524-532.
41. Rafnar, T. et al. 2009. Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat. Genet. 41: 221-227.
42. Kim, N.W. et al. 1994. Specific association of human telomerase activity with immortal cells and cancer. Science 266: 2011-2015.
43. Jeffreys, A.J., A. Ritchie & R. Neumann. 2000. High resolution analysis of haplotype diversity and mei-otic crossover in the human TAP2 recombination hotspot. Hum. Mol. Genet. 9: 725-733.
44. Rufer, N. et al. 1998. Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry. Nat. Biotechnol. 16: 743-747. (Pubitemid 28363755)
45. Baerlocher, G.M. et al. 2006. Flow cytometry and FISH to measure the average length of telomeres (flow FISH). Nat. Protoc. 1: 2365-2376.
46. Hasty, P. et al. 2003. Aging and genome maintenance: lessons from the mouse? Science 299: 1355-1359.
47. Notaro, R. et al. 1997. In vivo telomere dynamics of human hematopoietic stem cells. Proc. Natl. Acad. Sci. USA 94: 13782-13785.
48. Britt-Compton, B. et al. 2006. Structural stability and chromosome-specific telomere length is governed by cis-acting determinants in humans. Hum. Mol. Genet. 15: 725-733.
49. Martens, U.M. et al. 1998. Short telomeres on human chromosome 17p. Nat. Genet. 18: 76-80.
50. Kang, 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 Genet. Cytogenet. 182: 1-11.
51. Loeb, L.A., J.H. Bielas & R.A. Beckman. 2008. Cancers exhibit a mutator phenotype: clinical implications. Cancer Res. 68: 3551-3557; discussion 3557.
52. Hiyama, K. et al. 1995. Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J. Immunol. 155: 3711-3715.
53. Tsakiri, K.D. et al. 2007. Adult-onset pulmonary fi-brosis caused by mutations in telomerase. Proc. Natl. Acad. Sci. USA 104: 7552-7557.
54. Ortmann, C.A. et al. 2006. TERC mutations in children with refractory cytopenia. Haematologica 91: 707-708.
55. Marrone, A. et al. 2004. Heterozygous telomerase RNA mutations found in dyskeratosis congenita and aplastic anemia reduce telomerase activity via hap-loinsufficiency. Blood 104: 3936-3942.
56. Vulliamy, T. et al. 2002. Association between aplastic anaemia and mutations in telomerase RNA. Lancet 359: 2168-2170.
57. Vulliamy, T. et al. 2004. Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. Nat. Genet. 36: 447-449.
58. Liang, J. et al. 2006. Mutations in telomerase catalytic protein in Japanese children with aplastic anemia. Haematologica 91: 656-658.
59. Du, H.Y. et al. 2008. Complex inheritance pattern of dyskeratosis congenita in two families with 2 different mutations in the telomerase reverse transcriptase gene. Blood 111: 1128-1130.
60. Fogarty, P.F. et al. 2003. Late presentation of dysker-atosis congenita as apparently acquired aplastic anaemia due to mutations in telomerase RNA. Lancet 362: 1628-1630.
61. Vulliamy, T.J. et al. 2006. Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation. Blood 107: 2680-2685.
62. Quarto, R., D. Thomas & C.T. Liang. 1995. Bone progenitor cell deficits and the age-associated decline in bone repair capacity. Calcif. Tissue Int. 56: 123-129.
63. Ly, H. et al. 2005. Identification and functional characterization of 2 variant alleles of the telomerase RNA template gene (TERC) in a patient with dysker-atosis congenita. Blood. 106: 1246-1252.
64. Alter, B.P., N. Giri, S.A. Savage, et al. 2009. Cancer in dyskeratosis congenita. Blood, in press.