The potential utility of telomere-related markers for cancer diagnosis

J Cell Mol Med. 2011 Jun;15(6):1227-38. doi: 10.1111/j.1582-4934.2011.01284.x.

Abstract

The role telomeres and telomerase play in the initiation and progression of human cancers has been extensively evaluated. Telomeres are nucleoprotein complexes comprising the hexanucleotide DNA repeat sequence, TTAGGG and numerous telomere-associated proteins, including the six member Shelterin complex. The main function of the telomere is to stabilize the ends of the chromosomes. However, through multiple mechanisms, telomeres can become dysfunctional, which may drive genomic instability leading to the development of cancer. The majority of human cancers maintain, or actively lengthen, telomeres through up-regulation of the reverse transcriptase telomerase. Because there are significant differences in telomere length and telomerase activity between malignant and non-malignant tissues, many investigations have assessed the potential to utilize these molecular markers for cancer diagnosis. Here, we critically evaluate whether measurements of telomere lengths and telomerase levels may be clinically utilized as diagnostic markers in solid tumours, with emphasis on breast and prostate cancer as representative examples. Future directions focusing on the direct detection of dysfunctional telomeres are explored. New markers for telomere dysfunction may eventually prove clinically useful.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Biomarkers / analysis
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Chemistry Techniques, Analytical
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genomic Instability
  • Humans
  • Male
  • Minisatellite Repeats
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Shelterin Complex
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Telomere / metabolism*
  • Telomere / pathology
  • Telomere-Binding Proteins / genetics*
  • Telomere-Binding Proteins / metabolism
  • Up-Regulation

Substances

  • Biomarkers
  • Shelterin Complex
  • Telomere-Binding Proteins
  • Telomerase