DNA repair and replication proteins as prognostic markers in melanoma

Liang Song, Tammy Robson, Tamasin Doig, Thomas Brenn, Marie Mathers, Ewan R. Brown, Val Doherty, John M. S. Bartlett, Niall Anderson, David W. Melton

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: Elevated expression of DNA repair and replication genes has been reported in thick, non-fixed primary melanomas that subsequently went on to metastasize, when compared to non-recurrent primary tumours. This increased expression could contribute to the extreme resistance shown by melanoma to DNA-damaging chemotherapeutics. We have investigated the hypothesis that levels of key DNA repair and replication proteins are prognostic biomarkers in melanoma.
Methods and results: We used a tissue microarray containing samples from all stages of melanomagenesis to investigate the hypothesis that levels of key DNA repair and replication proteins are prognostic biomarkers in a larger, more representative and readily available set of fixed primary melanomas. High expression of topoisomerase IIa (TOP2A), that relieves torsional stress during DNA replication, and XRCC5 (Ku80), required for DNA double-strand break repair, were associated with significantly worse survival.
Conclusions: Two (XRCC5 and TOP2A) of seven DNA repair and replication proteins studied were prognostic for melanoma.

Original languageEnglish
Pages (from-to)343-350
Number of pages8
JournalHistopathology
Volume62
Issue number2
DOIs
Publication statusPublished - Jan 2013

Keywords

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA Helicases
  • DNA Repair
  • DNA Topoisomerases, Type II
  • DNA-Binding Proteins
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Great Britain
  • Humans
  • Kaplan-Meier Estimate
  • Lymph Nodes
  • Male
  • Melanoma
  • Prognosis
  • Proportional Hazards Models
  • Skin Neoplasms
  • Survival Rate
  • Tissue Array Analysis

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