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Telomere dysfunction, genome instability and cancer.

Annie L M Cheung1, Wen Deng

  • 1Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. lmcheung@hkucc.hku.hk

Frontiers in Bioscience : a Journal and Virtual Library
|November 6, 2007
PubMed
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Telomere dysfunction can cause genomic instability, leading to cancer development. Cells surviving crisis either activate telomerase or use alternative lengthening mechanisms to stabilize telomeres and prevent further instability.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cell Biology

Background:

  • Telomeres protect chromosome ends from damage and fusion.
  • Telomere length is maintained by telomerase, which is typically inactive in normal somatic cells.
  • Telomere attrition in telomerase-negative cells triggers senescence, a protective mechanism against uncontrolled proliferation.

Purpose of the Study:

  • To review the association between telomere dysfunction, genomic instability, and cancer.
  • To elucidate the mechanisms by which telomere dysfunction contributes to cancer development.

Main Methods:

  • This review synthesizes existing research on telomere biology and cancer.
  • Key concepts discussed include telomere structure, telomere maintenance mechanisms, and chromosomal instability.

Related Experiment Videos

  • The review examines the role of telomere dysfunction in initiating and propagating genetic aberrations characteristic of cancer.

    • Main Results:

    • Telomere dysfunction can lead to chromosomal instability through mechanisms like end-to-end fusions and breakage-fusion-bridge cycles.
    • This instability generates genetic aberrations, including aneuploidy and gene amplification, which are hallmarks of cancer.
    • Cells that survive crisis often achieve immortality by reactivating telomerase or employing alternative telomere lengthening (ALT) pathways.

    Conclusions:

    • Telomere dysfunction is a critical factor in initiating genomic instability and driving cancer development.
    • The ability of cells to overcome crisis through telomere stabilization is a key step in malignant transformation.
    • Understanding telomere maintenance and its link to genomic instability offers insights into cancer prevention and therapy.