title: Correlations of telomere length, telomerase activity, and telomeric-repeat binding factor 1 expression in colorectal carcinoma.
abstract: BACKGROUND
  Telomere maintenance has been proposed as an essential step for tumor cell immortalization. The objectives of the current study were to investigate the mechanisms implicated in telomere length in colorectal carcinoma (CRC) and to evaluate the prognostic impact of telomere status.
  
  
  METHODS
  Ninety-one colorectal carcinoma samples that were obtained from patients who underwent surgery were analyzed to investigate the factors related to telomere function. The authors studied telomerase activity, terminal restriction fragment (TRF) length, and telomeric-repeat binding factor (TRF1) expression and analyzed the prognostic implications of those factors.
  
  
  RESULTS
  Most tumors (81.3%) displayed telomerase activity. Overall, telomeres in CRC specimens were significantly shorter compared with telomeres in normal, adjacent specimens (P=0.02). Moreover, tumors that demonstrated shortened telomeres displayed higher TRF1 levels than tumors without telomere shortening. In relation to patient prognosis, a significantly poor clinical course was observed in the group of patients who had tumors with longer telomeres (P=0.02), and this finding emerged as an independent prognostic factor in a Cox proportional hazards model (P=0.04; relative risk, 6.48). Among patients with tumors classified as telomerase-positive, telomere length ratios (the ratio of tumor tissues to normal tissues)<or=0.66 or TRF1 over-expression conferred a favorable outcome (P=0.03 and P=0.05, respectively).
  
  
  CONCLUSIONS
  The majority of CRC specimens in the current study displayed telomerase reactivation. However, only those tumors that displayed telomere elongation conferred a poor prognosis. Conversely, colorectal tumors that over-expressed TRF1 demonstrated telomere shortening, and patients with those tumors had a better clinical course.
authors.affiliation: Departamento de Bioquimica y Biologia Molecular, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Garcia-Aranda
authors.forename: Carmen
authors.initials: C
authors.lastname: de Juan
authors.forename: Antonio
authors.initials: A
authors.lastname: Diaz-Lopez
authors.forename: Andres
authors.initials: A
authors.lastname: Sanchez-Pernaute
authors.forename: Antonio-Jose
authors.initials: AJ
authors.lastname: Torres
authors.forename: Eduardo
authors.initials: E
authors.lastname: Diaz-Rubio
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Balibrea
authors.forename: Manuel
authors.initials: M
authors.lastname: Benito
authors.forename: Pilar
authors.initials: P
authors.lastname: Iniesta
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000648:ultrastructure*; D035321:Telomeric Repeat Binding Protein 1 / Q000096:biosynthesis*
chemical_list: D035321:Telomeric Repeat Binding Protein 1; D019098:Telomerase