| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Oncology, Markers, Clinical Correlates |
1 Brady Urological Institute, and Departments of 2 Pathology and 3 Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
ABSTRACT
Purpose: Telomeres help maintain chromosomal integrity. Dysfunctional telomeres can cause genetic instability in vitro and an increased cancer incidence in telomerase knock out mouse models. We recently reported that telomere shortening was a prevalent alteration in human prostate, pancreas, and breast cancer precursor lesions. In the present study, we address whether the previous findings are broadly applicable to human epithelial cancer precursors in general.
Experimental Design: Surgical specimens of epithelial cancer precursor lesions from the urinary bladder, esophagus, large intestine, oral cavity, and uterine cervix were examined using a recently developed technique for direct in situ telomere length assessment in formalin-fixed human tissue specimens.
Results: Widespread telomere length abnormalities were nearly universal (97.1% of cases) in the preinvasive stages of human epithelial carcinogenesis in all sites examined in this series, with telomere shortening the predominant abnormality (88.6% of cases).
Conclusions: Telomere length abnormalities appear to be one of the earliest and most prevalent genetic alterations acquired in the multistep process of malignant transformation. These findings support a model whereby telomere dysfunction induces chromosomal instability as an initiating event in many, perhaps most, human epithelial cancers. Together with previous findings from the prostate and pancreas, the percentage of intraepithelial neoplasia lesions showing telomere length abnormalities is 95.6%. The implications of these findings include the potential that telomere length assessment in situ may be a widely useful biomarker for monitoring disease prevention strategies and for improved early diagnosis.
This article has been cited by other articles:
|
|
 |
|
  R. A. Risques, T. L. Vaughan, X. Li, R. D. Odze, P. L. Blount, K. Ayub, J. L. Gallaher, B. J. Reid, and P. S. Rabinovitch Leukocyte Telomere Length Predicts Cancer Risk in Barrett's Esophagus Cancer Epidemiol. Biomarkers Prev., December 1, 2007; 16(12): 2649 - 2655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Morton, S. Zhang, A. Lopez-Beltran, G. T. MacLennan, J. N. Eble, R. Montironi, M.-T. Sung, P.-H. Tan, S. Zheng, H. Zhou, et al. Telomere Shortening and Chromosomal Abnormalities in Intestinal Metaplasia of the Urinary Bladder Clin. Cancer Res., October 15, 2007; 13(20): 6232 - 6236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Souza, T. Lunsford, R. D. Ramirez, X. Zhang, E. L. Lee, Y. Shen, C. Owen, J. W. Shay, C. Morales, and S. J. Spechler GERD is associated with shortened telomeres in the squamous epithelium of the distal esophagus Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G19 - G24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Shen, M. B. Terry, I. Gurvich, Y. Liao, R. T. Senie, and R. M. Santella Short Telomere Length and Breast Cancer Risk: A Study in Sister Sets Cancer Res., June 1, 2007; 67(11): 5538 - 5544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. McGrath, J. Y.Y. Wong, D. Michaud, D. J. Hunter, and I. De Vivo Telomere Length, Cigarette Smoking, and Bladder Cancer Risk in Men and Women Cancer Epidemiol. Biomarkers Prev., April 1, 2007; 16(4): 815 - 819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Jin, Y. Stewenius, D. Lindgren, A. Frigyesi, O. Calcagnile, T. Jonson, A. Edqvist, N. Larsson, L. M. Lundberg, G. Chebil, et al. Distinct Mitotic Segregation Errors Mediate Chromosomal Instability in Aggressive Urothelial Cancers Clin. Cancer Res., March 15, 2007; 13(6): 1703 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Finley, B. J. Reid, R. D. Odze, C. A. Sanchez, P. Galipeau, X. Li, S. G. Self, K. A. Gollahon, P. L. Blount, and P. S. Rabinovitch Chromosomal Instability in Barrett's Esophagus Is Related to Telomere Shortening. Cancer Epidemiol. Biomarkers Prev., August 1, 2006; 15(8): 1451 - 1457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Hochreiter, H. Xiao, E. M. Goldblatt, S. M. Gryaznov, K. D. Miller, S. Badve, G. W. Sledge, and B.-S. Herbert Telomerase Template Antagonist GRN163L Disrupts Telomere Maintenance, Tumor Growth, and Metastasis of Breast Cancer. Clin. Cancer Res., May 15, 2006; 12(10): 3184 - 3192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jimeno and M. Hidalgo Molecular biomarkers: their increasing role in the diagnosis, characterization, and therapy guidance in pancreatic cancer. Mol. Cancer Ther., April 1, 2006; 5(4): 787 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Bailey and J. P. Murnane Telomeres, chromosome instability and cancer. Nucleic Acids Res., January 1, 2006; 34(8): 2408 - 2417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Broberg, J. Bjork, K. Paulsson, M. Hoglund, and M. Albin Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer Carcinogenesis, July 1, 2005; 26(7): 1263 - 1271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sabatier, M. Ricoul, G. Pottier, and J. P. Murnane The Loss of a Single Telomere Can Result in Instability of Multiple Chromosomes in a Human Tumor Cell Line Mol. Cancer Res., March 1, 2005; 3(3): 139 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Schroecksnadel, F. Ueberall, and D. Fuchs Telomere Length Abnormalities and Human Cancer Clin. Cancer Res., January 15, 2005; 11(2): 860 - 860. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Cell Growth & Differentiation |
