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Replicative Cell Senescence02:15

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Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
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Telomere maintenance and dysfunction predict recurrence in paediatric ependymoma.

U Tabori1, V Wong, J Ma

  • 1Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

British Journal of Cancer
|September 18, 2008
PubMed
Summary

Human telomerase reverse transcriptase (hTERT) expression and telomere dysfunction are key prognostic markers for pediatric ependymoma. High hTERT expression with no DNA damage indicates the worst outcome, suggesting telomerase inhibition as a therapeutic target.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Pediatric ependymoma lacks robust preclinical models, necessitating direct patient cohort studies.
  • Human telomerase reverse transcriptase (hTERT) has emerged as a significant prognostic marker in pediatric ependymoma.

Purpose of the Study:

  • To investigate telomere biology and its correlation with clinical outcomes in a large cohort of pediatric ependymoma patients.
  • To explore the prognostic value of hTERT expression and telomere dysfunction in relation to tumor progression and survival.

Main Methods:

  • Analysis of 133 ependymomas from 83 pediatric patients, including those with multiple recurrences.
  • Correlation of hTERT expression with proliferative markers (MIB-1, mitotic index) and tumor grade.
  • Assessment of telomere length, DNA damage (gamma H2AX), and their relationship with hTERT expression and patient survival.

Main Results:

  • hTERT expression correlated with proliferative markers and tumor grade, but not anaplasia markers.
  • No correlation was found between telomere length and hTERT expression or survival.
  • Inverse correlation between hTERT expression and telomere dysfunction (gamma H2AX).
  • Combined analysis of gamma H2AX and hTERT expression identified three distinct survival groups (log rank, P<0.0001).
  • Patients with hTERT-expressing tumors and no DNA damage exhibited the poorest survival outcomes.

Conclusions:

  • Telomere biology, specifically hTERT expression and telomere dysfunction, serves as a crucial prognostic tool in pediatric ependymoma.
  • Telomerase inhibition presents a potential therapeutic strategy for pediatric ependymoma.
  • In vivo analysis of tumor progression in human patients is a feasible approach for studying tumor biology.