title: DNA repair and replication proteins as prognostic markers in melanoma.
abstract: OBJECTIVE
  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.
  
  
  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 IIα (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.
authors.affiliation: Edinburgh Cancer Research Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: Liang
authors.initials: L
authors.lastname: Song
authors.forename: Tammy
authors.initials: T
authors.lastname: Robson
authors.forename: Tamasin
authors.initials: T
authors.lastname: Doig
authors.forename: Thomas
authors.initials: T
authors.lastname: Brenn
authors.forename: Marie
authors.initials: M
authors.lastname: Mathers
authors.forename: Ewan R
authors.initials: ER
authors.lastname: Brown
authors.forename: Val
authors.initials: V
authors.lastname: Doherty
authors.forename: John M S
authors.initials: JM
authors.lastname: Bartlett
authors.forename: Niall
authors.initials: N
authors.lastname: Anderson
authors.forename: David W
authors.initials: DW
authors.lastname: Melton
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D000072200:Ku Autoantigen; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D046888:Tissue Array Analysis; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004265:DNA Helicases; C106893:XRCC5 protein, human; D000072200:Ku Autoantigen; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human