The potential utility of telomere-related markers for cancer diagnosis

Journal of Cellular and Molecular Medicine

Volumn 15, Issue 6, 2011, Pages 1227-1238

  Heaphy, Christopher M ^a   Meeker, Alan K ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Breast cancer; Cancer; Detection; Diagnosis; Prostate cancer; Telomerase; Telomere; Telomere dysfunction

Indexed keywords

BIOLOGICAL MARKER; SHELTERIN, HUMAN; TELOMERASE; TELOMERE BINDING PROTEIN;

ARTICLE; BREAST TUMOR; CHEMICAL ANALYSIS; DISEASE COURSE; FEMALE; GENE EXPRESSION REGULATION; GENETICS; GENOMIC INSTABILITY; HUMAN; MALE; METABOLISM; PATHOLOGY; PROSTATE TUMOR; TELOMERE; UPREGULATION; VARIABLE NUMBER OF TANDEM REPEAT;

BIOLOGICAL MARKERS; BREAST NEOPLASMS; CHEMISTRY TECHNIQUES, ANALYTICAL; DISEASE PROGRESSION; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENOMIC INSTABILITY; HUMANS; MALE; MINISATELLITE REPEATS; PROSTATIC NEOPLASMS; TELOMERASE; TELOMERE; TELOMERE-BINDING PROTEINS; UP-REGULATION;

EID: 79957668093     PISSN: 15821838     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1582-4934.2011.01284.x     Document Type: Article

References (140)

1. Blackburn EH. Structure and function of telomeres. Nature. 1991; 350: 569-73.
2. Meyne J, Ratliff RL, Moyzis RK. Conservation of the human telomere sequence (TTAGGG)n among vertebrates. Proc Natl Acad Sci USA. 1989; 86: 7049-53.
3. Moyzis RK, Buckingham JM, Cram LS, et al A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci USA. 1988; 85: 6622-6.
4. Palm W, de Lange T. How Shelterin protects mammalian telomeres. Annu Rev Genet. 2008; 42: 301-34.
5. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005; 19: 2100-10.
6. de Lange T. How telomeres solve the end-protection problem. Science. 2009; 326: 948-52.
7. O'Sullivan RJ, Karlseder J. Telomeres: protecting chromosomes against genome instability. Nat Rev Mol Cell Biol. 2010; 11: 171-81.
8. Olovnikov AM. [Principle of marginotomy in template synthesis of polynucleotides]. Dokl Akad Nauk SSSR. 1971; 201: 1496-9.
9. de Lange T. How Shelterin solves the telomere end-protection problem. Cold Spring Harb Symp Quant Biol. 2011; DOI:.
10. Bohr VA, Anson RM. DNA damage, mutation and fine structure DNA repair in aging. Mutat Res. 1995; 338: 25-34.
11. von Zglinicki T, Pilger R, Sitte N. Accumulation of single-strand breaks is the major cause of telomere shortening in human fibroblasts. Free Radic Biol Med. 2000; 28: 64-74.
12. Smogorzewska A, de Lange T. Regulation of telomerase by telomeric proteins. Annu Rev Biochem. 2004; 73: 177-208.
13. Vaziri H. Critical telomere shortening regulated by the ataxia-telangiectasia gene acts as a DNA damage signal leading to activation of p53 protein and limited life-span of human diploid fibroblasts. A review. Biochemistry. 1997; 62: 1306-10.
14. d'Adda di Fagagna F, Reaper PM, Clay-Farrace L, et al A DNA damage checkpoint response in telomere-initiated senescence. Nature. 2003; 426: 194-8.
15. Maser RS, DePinho RA. Connecting chromosomes, crisis, and cancer. Science. 2002; 297: 565-9.
16. McClintock B. The fusion of broken ends of chromosomes following nuclear fusion. Proc Natl Acad Sci USA. 1942; 28: 458-63.
17. Allsopp RC, Vaziri H, Patterson C, et al Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA. 1992; 89: 10114-8.
18. Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell. 1985; 43: 405-13.
19. Greider CW, Blackburn EH. A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature. 1989; 337: 331-7.
20. Shippen-Lentz D, Blackburn EH. Functional evidence for an RNA template in telomerase. Science. 1990; 247: 546-52.
21. Nakamura TM, Morin GB, Chapman KB, et al Telomerase catalytic subunit homologs from fission yeast and human. Science. 1997; 277: 955-9.
22. Feng J, Funk WD, Wang SS, et al The RNA component of human telomerase. Science. 1995; 269: 1236-41.
23. Cesare AJ, Reddel RR. Alternative lengthening of telomeres: models, mechanisms and implications. Nat Rev Genet. 2010; 11: 319-30.
24. Bisoffi M, Heaphy CM, Griffith JK. Telomeres: prognostic markers for solid tumors. Int J Cancer. 2006; 119: 2255-60.
25. Svenson U, Roos G. Telomere length as a biological marker in malignancy. Biochim Biophys Acta. 2009; 1792: 317-23.
26. Keller G, Brassat U, Braig M, et al Telomeres and telomerase in chronic myeloid leukaemia: impact for pathogenesis, disease progression and targeted therapy. Hematol Oncol. 2009; 27: 123-9.
27. Gancarcikova M, Zemanova Z, Brezinova J, et al The role of telomeres and telomerase complex in haematological neoplasia: the length of telomeres as a marker of carcinogenesis and prognosis of disease. Prague Med Rep. 2010; 111: 91-105.
28. Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990; 345: 458-60.
29. Hastie ND, Dempster M, Dunlop MG, et al Telomere reduction in human colorectal carcinoma and with ageing. Nature. 1990; 346: 866-8.
30. Lansdorp PM, Verwoerd NP, van de Rijke FM, et al Heterogeneity in telomere length of human chromosomes. Hum Mol Genet. 1996; 5: 685-91.
31. O'Sullivan JN, Bronner MP, Brentnall TA, et al Chromosomal instability in ulcerative colitis is related to telomere shortening. Nat Genet. 2002; 32: 280-4.
32. Meeker AK, Gage WR, Hicks JL, et al Telomere length assessment in human archival tissues: combined telomere fluorescence in situ hybridization and immunostaining. Am J Pathol. 2002; 160: 1259-68.
33. Rufer N, Dragowska W, Thornbury G, et al Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry. Nat Biotechnol. 1998; 16: 743-7.
34. Bryant JE, Hutchings KG, Moyzis RK, et al Measurement of telomeric DNA content in human tissues. Biotechniques. 1997; 23: 476-80, 82.
35. Fordyce CA, Heaphy CM, Griffith JK. Chemiluminescent measurement of telomere DNA content in biopsies. Biotechniques. 2002; 33: 144-6, 8.
36. Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002; 30: 1-6.
37. Cawthon RM. Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res. 2009; 37: 1-7.
38. Baird DM, Rowson J, Wynford-Thomas D, et al Extensive allelic variation and ultrashort telomeres in senescent human cells. Nat Genet. 2003; 33: 203-7.
39. Kim NW, Piatyszek MA, Prowse KR, et al Specific association of human telomerase activity with immortal cells and cancer. Science. 1994; 266: 2011-5.
40. Odagiri E, Kanada N, Jibiki K, et al Reduction of telomeric length and c-erbB-2 gene amplification in human breast cancer, fibroadenoma, and gynecomastia. Relationship to histologic grade and clinical parameters. Cancer. 1994; 73: 2978-84.
41. Rha SY, Park KH, Kim TS, et al Changes of telomerase and telomere lengths in paired normal and cancer tissues of breast. Int J Oncol. 1999; 15: 839-45.
42. Rogalla P, Rohen C, Bonk U, et al Telomeric repeat fragment lengths are not correlated to histological grading in 85 breast cancers. Cancer Lett. 1996; 106: 155-61.
43. Griffith JK, Bryant JE, Fordyce CA, et al Reduced telomere DNA content is correlated with genomic instability and metastasis in invasive human breast carcinoma. Breast Cancer Res Treat. 1999; 54: 59-64.
44. Meeker AK, Hicks JL, Gabrielson E, et al Telomere shortening occurs in subsets of normal breast epithelium as well as in situ and invasive carcinoma. Am J Pathol. 2004; 164: 925-35.
45. Bryan TM, Englezou A, Dalla-Pozza L, et al Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat Med. 1997; 3: 1271-4.
46. Subhawong AP, Heaphy CM, Argani P, et al The alternative lengthening of telomeres phenotype in breast carcinoma is associated with HER-2 overexpression. Mod Pathol. 2009; 22: 1423-31.
47. Henson JD, Reddel RR. Assaying and investigating Alternative Lengthening of Telomeres activity in human cells and cancers. FEBS Lett. 2010; 584: 3800-11.
48. Meeker AK, Argani P. Telomere shortening occurs early during breast tumorigenesis: a cause of chromosome destabilization underlying malignant transformation? J Mammary Gland Biol Neoplasia. 2004; 9: 285-96.
49. Kurabayashi R, Takubo K, Aida J, et al Luminal and cancer cells in the breast show more rapid telomere shortening than myoepithelial cells and fibroblasts. Hum Pathol. 2008; 39: 1647-55.
50. Heaphy CM, Bisoffi M, Fordyce CA, et al Telomere DNA content and allelic imbalance demonstrate field cancerization in histologically normal tissue adjacent to breast tumors. Int J Cancer. 2006; 119: 108-16.
51. Dakubo GD, Jakupciak JP, Birch-Machin MA, et al Clinical implications and utility of field cancerization. Cancer Cell Int. 2007; 7: 2.
52. Heaphy CM, Griffith JK, Bisoffi M. Mammary field cancerization: molecular evidence and clinical importance. Breast Cancer Res Treat. 2009; 118: 229-39.
53. Shen J, Gammon MD, Terry MB, et al Telomere length, oxidative damage, antioxidants and breast cancer risk. Int J Cancer. 2009; 124: 1637-43.
54. Shen J, Terry MB, Gurvich I, et al Short telomere length and breast cancer risk: a study in sister sets. Cancer Res. 2007; 67: 5538-44.
55. Zheng YL, Ambrosone C, Byrne C, et al Telomere length in blood cells and breast cancer risk: investigations in two case-control studies. Breast Cancer Res Treat. 2010; 120: 769-75.
56. Barwell J, Pangon L, Georgiou A, et al Is telomere length in peripheral blood lymphocytes correlated with cancer susceptibility or radiosensitivity? Br J Cancer. 2007; 97: 1696-700.
57. Svenson U, Nordfjall K, Stegmayr B, et al Breast cancer survival is associated with telomere length in peripheral blood cells. Cancer Res. 2008; 68: 3618-23.
58. Gramatges MM, Telli ML, Balise R, et al Longer relative telomere length in blood from women with sporadic and familial breast cancer compared with healthy controls. Cancer Epidemiol Biomarkers Prev. 2010; 19: 605-13.
59. De Vivo I, Prescott J, Wong JY, et al A prospective study of relative telomere length and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2009; 18: 1152-6.
60. Pooley KA, Sandhu MS, Tyrer J, et al Telomere length in prospective and retrospective cancer case-control studies. Cancer Res. 2010; 70: 3170-6.
61. Zheng YL, Loffredo CA, Shields PG, et al Chromosome 9 arm-specific telomere length and breast cancer risk. Carcinogenesis. 2009; 30: 1380-6.
62. Zheng YL, Zhou X, Loffredo CA, et al Telomere deficiencies on chromosomes 9p, 15p, 15q and Xp: potential biomarkers for breast cancer risk. Hum Mol Genet. 2011; 20: 378-86.
63. Sommerfeld HJ, Meeker AK, Piatyszek MA, et al Telomerase activity: a prevalent marker of malignant human prostate tissue. Cancer Res. 1996; 56: 218-22.
64. Engelhardt M, Albanell J, Drullinsky P, et al Relative contribution of normal and neoplastic cells determines telomerase activity and telomere length in primary cancers of the prostate, colon, and sarcoma. Clin Cancer Res. 1997; 3: 1849-57.
65. Koeneman KS, Pan CX, Jin JK, et al Telomerase activity, telomere length, and DNA ploidy in prostatic intraepithelial neoplasia (PIN). J Urol. 1998; 160: 1533-9.
66. Donaldson L, Fordyce C, Gilliland F, et al Association between outcome and telomere DNA content in prostate cancer. J Urol. 1999; 162: 1788-92.
67. Meeker AK, Hicks JL, Platz EA, et al Telomere shortening is an early somatic DNA alteration in human prostate tumorigenesis. Cancer Res. 2002; 62: 6405-9.
68. Vukovic B, Park PC, Al-Maghrabi J, et al Evidence of multifocality of telomere erosion in high-grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma. Oncogene. 2003; 22: 1978-87.
69. Fordyce CA, Heaphy CM, Joste NE, et al Association between cancer-free survival and telomere DNA content in prostate tumors. J Urol. 2005; 173: 610-4.
70. Treat EG, Heaphy CM, Massie LW, et al Telomere DNA content in prostate biopsies predicts early rise in prostate-specific antigen after radical prostatectomy for prostate cancer. Urology. 2010; 75: 724-9.
71. Mirabello L, Huang WY, Wong JY, et al The association between leukocyte telomere length and cigarette smoking, dietary and physical variables, and risk of prostate cancer. Aging Cell. 2009; 8: 405-13.
72. Joshua AM, Vukovic B, Braude I, et al Telomere attrition in isolated high-grade prostatic intraepithelial neoplasia and surrounding stroma is predictive of prostate cancer. Neoplasia. 2007; 9: 81-9.
73. Heaphy CM, Fleet TM, Treat EG, et al Organ-wide telomeric status in diseased and disease-free prostatic tissues. Prostate. 2010; 70: 1471-9.
74. Joshua AM, Shen E, Yoshimoto M, et al Topographical analysis of telomere length and correlation with genomic instability in whole mount prostatectomies. Prostate. 2010; DOI.
75. Gertler R, Rosenberg R, Stricker D, et al Telomere length and human telomerase reverse transcriptase expression as markers for progression and prognosis of colorectal carcinoma. J Clin Oncol. 2004; 22: 1807-14.
76. Garcia-Aranda C, de Juan C, Diaz-Lopez A, et al Correlations of telomere length, telomerase activity, and telomeric-repeat binding factor 1 expression in colorectal carcinoma. Cancer. 2006; 106: 541-51.
77. Meeker AK, Hicks JL, Iacobuzio-Donahue CA, et al Telomere length abnormalities occur early in the initiation of epithelial carcinogenesis. Clin Cancer Res. 2004; 10: 3317-26.
78. van Heek NT, Meeker AK, Kern SE, et al Telomere shortening is nearly universal in pancreatic intraepithelial neoplasia. Am J Pathol. 2002; 161: 1541-7.
79. Harley CB. Telomerase and cancer therapeutics. Nat Rev Cancer. 2008; 8: 167-79.
80. Hou L, Savage SA, Blaser MJ, et al Telomere length in peripheral leukocyte DNA and gastric cancer risk. Cancer Epidemiol Biomarkers Prev. 2009; 18: 3103-9.
81. Mirabello L, Garcia-Closas M, Cawthon R, et al Leukocyte telomere length in a population-based case-control study of ovarian cancer: a pilot study. Cancer Causes Control. 2010; 21: 77-82.
82. Lan Q, Cawthon R, Shen M, et al A prospective study of telomere length measured by monochrome multiplex quantitative PCR and risk of non-Hodgkin lymphoma. Clin Cancer Res. 2009; 15: 7429-33.
83. Zee RY, Castonguay AJ, Barton NS, et al Mean telomere length and risk of incident colorectal carcinoma: a prospective, nested case-control approach. Cancer Epidemiol Biomarkers Prev. 2009; 18: 2280-2.
84. Lee IM, Lin J, Castonguay AJ, et al Mean leukocyte telomere length and risk of incident colorectal carcinoma in women: a prospective, nested case-control study. Clin Chem Lab Med. 2010; 48: 259-62.
85. Willeit P, Willeit J, Mayr A, et al Telomere length and risk of incident cancer and cancer mortality. JAMA. 2010; 304: 69-75.
86. Hiyama E, Gollahon L, Kataoka T, et al Telomerase activity in human breast tumors. J Natl Cancer Inst. 1996; 88: 116-22.
87. Sugino T, Yoshida K, Bolodeoku J, et al Telomerase activity in human breast cancer and benign breast lesions: diagnostic applications in clinical specimens, including fine needle aspirates. Int J Cancer. 1996; 69: 301-6.
88. Bednarek AK, Sahin A, Brenner AJ, et al Analysis of telomerase activity levels in breast cancer: positive detection at the in situ breast carcinoma stage. Clin Cancer Res. 1997; 3: 11-6.
89. Tsao J, Zhao Y, Lukas J, et al Telomerase activity in normal and neoplastic breast. Clin Cancer Res. 1997; 3: 627-31.
90. Yashima K, Milchgrub S, Gollahon LS, et al Telomerase enzyme activity and RNA expression during the multistage pathogenesis of breast carcinoma. Clin Cancer Res. 1998; 4: 229-34.
91. Poremba C, Bocker W, Willenbring H, et al Telomerase activity in human proliferative breast lesions. Int J Oncol. 1998; 12: 641-8.
92. Cunningham VJ, Markham N, Shroyer AL, et al Detection of telomerase expression in fine-needle aspirations and fluids. Diagn Cytopathol. 1998; 18: 431-6.
93. Poremba C, Shroyer KR, Frost M, et al Telomerase is a highly sensitive and specific molecular marker in fine-needle aspirates of breast lesions. J Clin Oncol. 1999; 17: 2020-6.
94. Hiyama E, Saeki T, Hiyama K, et al Telomerase activity as a marker of breast carcinoma in fine-needle aspirated samples. Cancer. 2000; 90: 235-8.
95. Mokbel K, Williams NJ, Leris AC, et al Telomerase activity in fine-needle aspirates of breast lesions. J Clin Oncol. 1999; 17: 3856-60.
96. Kirkpatrick KL, Clark G, Ghilchick M, et al hTERT mRNA expression correlates with telomerase activity in human breast cancer. Eur J Surg Oncol. 2003; 29: 321-6.
97. Kirkpatrick KL, Ogunkolade W, Elkak AE, et al hTERT expression in human breast cancer and non-cancerous breast tissue: correlation with tumour stage and c-Myc expression. Breast Cancer Res Treat. 2003; 77: 277-84.
98. Salhab M, Jiang WG, Newbold RF, et al The expression of gene transcripts of telomere-associated genes in human breast cancer: correlation with clinico-pathological parameters and clinical outcome. Breast Cancer Res Treat. 2008; 109: 35-46.
99. Shen C, Hu L, Xia L, et al The detection of circulating tumor cells of breast cancer patients by using multimarker (Survivin, hTERT and hMAM) quantitative real-time PCR. Clin Biochem. 2009; 42: 194-200.
100. Divella R, Tommasi S, Lacalamita R, et al Circulating hTERT DNA in early breast cancer. Anticancer Res. 2009; 29: 2845-9.
101. Lin Y, Uemura H, Fujinami K, et al Telomerase activity in primary prostate cancer. J Urol. 1997; 157: 1161-5.
102. Meeker AK. Telomeres and telomerase in prostatic intraepithelial neoplasia and prostate cancer biology. Urol Oncol. 2006; 24: 122-30.
103. Wang Z, Ramin SA, Tsai C, et al Detection of telomerase activity in prostatic fluid specimens. Urol Oncol. 2000; 6: 4-9.
104. Meid FH, Gygi CM, Leisinger HJ, et al The use of telomerase activity for the detection of prostatic cancer cells after prostatic massage. J Urol. 2001; 165: 1802-5.
105. Vicentini C, Gravina GL, Angelucci A, et al Detection of telomerase activity in prostate massage samples improves differentiating prostate cancer from benign prostatic hyperplasia. J Cancer Res Clin Oncol. 2004; 130: 217-21.
106. Botchkina GI, Kim RH, Botchkina IL, et al Noninvasive detection of prostate cancer by quantitative analysis of telomerase activity. Clin Cancer Res. 2005; 11: 3243-9.
107. Crocitto LE, Korns D, Kretzner L, et al Prostate cancer molecular markers GSTP1 and hTERT in expressed prostatic secretions as predictors of biopsy results. Urology. 2004; 64: 821-5.
108. Pfitzenmaier J, Ellis WJ, Arfman EW, et al Telomerase activity in disseminated prostate cancer cells. BJU Int. 2006; 97: 1309-13.
109. Dasi F, Martinez-Rodes P, March JA, et al Real-time quantification of human telomerase reverse transcriptase mRNA in the plasma of patients with prostate cancer. Ann NY Acad Sci. 2006; 1075: 204-10.
110. Altimari A, Grigioni AD, Benedettini E, et al Diagnostic role of circulating free plasma DNA detection in patients with localized prostate cancer. Am J Clin Pathol. 2008; 129: 756-62.
111. Fizazi K, Morat L, Chauveinc L, et al High detection rate of circulating tumor cells in blood of patients with prostate cancer using telomerase activity. Ann Oncol. 2007; 18: 518-21.
112. Xu T, Lu B, Tai YC, Goldkorn A. A cancer detection platform which measures telomerase activity from live circulating tumor cells captured on a microfilter. Cancer Res. 2010; 70: 6420-6.
113. Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer. 1997; 33: 787-91.
114. Fernandez-Garcia I, Ortiz-de-Solorzano C, et al Telomeres and telomerase in lung cancer. J Thorac Oncol. 2008; 3: 1085-8.
115. Else T. Telomeres and telomerase in adrenocortical tissue maintenance, carcinogenesis, and aging. J Mol Endocrinol. 2009; 43: 131-41.
116. Eissa S, Swellam M, Ali-Labib R, et al Detection of telomerase in urine by 3 methods: evaluation of diagnostic accuracy for bladder cancer. J Urol. 2007; 178: 1068-72.
117. Bravaccini S, Sanchini MA, Granato AM, et al Urine telomerase activity for the detection of bladder cancer in females. J Urol. 2007; 178: 57-61.
118. Sanchini MA, Gunelli R, Nanni O, et al Relevance of urine telomerase in the diagnosis of bladder cancer. JAMA. 2005; 294: 2052-6.
119. Wu YL, Dudognon C, Nguyen E, et al Immunodetection of human telomerase reverse-transcriptase (hTERT) re-appraised: nucleolin and telomerase cross paths. J Cell Sci. 2006; 119: 2797-806.
120. Weir BA, Woo MS, Getz G, et al Characterizing the cancer genome in lung adenocarcinoma. Nature. 2007; 450: 893-8.
121. Beroukhim R, Mermel CH, Porter D, et al The landscape of somatic copy-number alteration across human cancers. Nature. 2010; 463: 899-905.
122. Pelosi G, Del Curto B, Trubia M, et al 3q26 Amplification and polysomy of chromosome 3 in squamous cell lesions of the lung: a fluorescence in situ hybridization study. Clin Cancer Res. 2007; 13: 1995-2004.
123. Heselmeyer-Haddad K, Sommerfeld K, White NM, et al Genomic amplification of the human telomerase gene (TERC) in pap smears predicts the development of cervical cancer. Am J Pathol. 2005; 166: 1229-38.
124. Andersson S, Sowjanya P, Wangsa D, et al Detection of genomic amplification of the human telomerase gene TERC, a potential marker for triage of women with HPV-positive, abnormal Pap smears. Am J Pathol. 2009; 175: 1831-47.
125. Jiang J, Wei LH, Li YL, et al Detection of TERC amplification in cervical epithelial cells for the diagnosis of high-grade cervical lesions and invasive cancer: a multicenter study in China. J Mol Diagn. 2010; 12: 808-17.
126. Rafnar T, Sulem P, Stacey SN, et al Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet. 2009; 41: 221-7.
127. McKay JD, Hung RJ, Gaborieau V, et al Lung cancer susceptibility locus at 5p15.33. Nat Genet. 2008; 40: 1404-6.
128. Petersen GM, Amundadottir L, Fuchs CS, et al A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet. 2010; 42: 224-8.
129. Wang Y, Broderick P, Webb E, et al Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet. 2008; 40: 1407-9.
130. Pooley KA, Tyrer J, Shah M, et al No association between TERT-CLPTM1L single nucleotide polymorphism rs401681 and mean telomere length or cancer risk. Cancer Epidemiol Biomarkers Prev. 2010; 19: 1862-5.
131. Baird DM. Variation at the TERT locus and predisposition for cancer. Expert Rev Mol Med. 2010; 12: e16.
132. Feldser DM, Hackett JA, Greider CW. Telomere dysfunction and the initiation of genome instability. Nat Rev Cancer. 2003; 3: 623-7.
133. Hemann MT, Strong MA, Hao LY, et al The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell. 2001; 107: 67-77.
134. Campbell PJ, Yachida S, Mudie LJ, et al The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature. 2010; 467: 1109-13.
135. Davoli T, Denchi EL, de Lange T. Persistent telomere damage induces bypass of mitosis and tetraploidy. Cell. 2010; 141: 81-93.
136. van Steensel B, Smogorzewska A, de Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell. 1998; 92: 401-13.
137. Celli GB, de Lange T. DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat Cell Biol. 2005; 7: 712-8.
138. Brault ME, Autexier C. Telomeric recombination induced by dysfunctional telomeres. Mol Biol Cell. 2011; 22: 179-88.
139. Sfeir A, Kabir S, van Overbeek M, et al Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signal. Science. 2010; 327: 1657-61.
140. Takai H, Smogorzewska A, de Lange T. DNA damage foci at dysfunctional telomeres. Curr Biol. 2003; 13: 1549-56.