title: Telomere shortening is associated with poor prognosis and telomerase activity correlates with DNA repair impairment in non-small cell lung cancer.
abstract: OBJECTIVE
  Telomere function and DNA damage response pathways are frequently inactivated in cancer. Moreover, some telomere-binding proteins have been implicated in DNA repair. The purpose of this work consists of evaluating the prognostic impact of telomere dysfunction and its relationship with DNA repair systems in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We analysed 83 NSCLCs and their corresponding control samples obtained from patients submitted to surgery. Telomere function was evaluated by determining telomerase activity and telomere length. DNA repair expression assays were established by using cDNA arrays containing 96 DNA-repair genes and by Real Time Quantitative PCR.
  
  
  RESULTS
  Our data indicated that telomere attrition was significantly associated with poor clinical outcome of patients (P=0.02), being this parameter a significant prognostic factor independent of tumour stage (P=0.012; relative risk=1.887; 95% CI: 1.147-3.102). DNA-repair gene expression studies showed down regulation of DCLRE1C and GTF2H1 and a clear FLJ10858 up regulation in tumour tissues, as compared to controls. In addition, a number of genes related to DNA-repair were significantly down regulated in tumours that reactivated telomerase (DCLRE1C, GTF2H1, PARP-3, MLH1, and TRF2).
  
  
  CONCLUSIONS
  Telomere shortening emerged as a poor clinical evolution parameter in NSCLC. Moreover, results from this work suggest a relationship between the loss of several DNA repair genes and telomerase activity, which may be of relevance in the pathogenesis of non-small lung cancer.
authors: Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad Complutense, 28040-Madrid, Spain.
authors: Cristina
authors: C
authors: Frías
authors: Cristina
authors: C
authors: García-Aranda
authors: Carmen
authors: C
authors: De Juan
authors: Alberto
authors: A
authors: Morán
authors: Paloma
authors: P
authors: Ortega
authors: Ana
authors: A
authors: Gómez
authors: Florentino
authors: F
authors: Hernando
authors: Jose-Antonio
authors: JA
authors: López-Asenjo
authors: Antonio-José
authors: AJ
authors: Torres
authors: Manuel
authors: M
authors: Benito
authors: Pilar
authors: P
authors: Iniesta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009699:N-Glycosyl Hydrolases / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D011379:Prognosis; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000201:enzymology* / Q000235:genetics; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics; D051758:Transcription Factor TFIIH; D019473:Transcription Factors, TFII / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C072546:GTF2H1 protein, human; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2; D019473:Transcription Factors, TFII; D051758:Transcription Factor TFIIH; C480979:PARP3 protein, human; D011065:Poly(ADP-ribose) Polymerases; D019098:Telomerase; C426344:DCLRE1C protein, human; D004720:Endonucleases; D009699:N-Glycosyl Hydrolases; C468764:NEIL3 protein, human; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes