title: Multiple mechanisms of telomere maintenance exist and differentially affect clinical outcome in diffuse malignant peritoneal mesothelioma.
abstract: OBJECTIVE
  This study aims to investigate the prevalence of the two known telomere maintenance mechanisms, telomerase activity (TA) and alternative lengthening of telomeres (ALT), and to assess their prognostic relevance in diffuse malignant peritoneal mesothelioma (DMPM).
  
  
  METHODS
  In 44 DMPM specimens obtained from 38 patients, TA was determined using the telomeric repeat amplification protocol and ALT was detected by assaying ALT-associated promyelocytic leukemia nuclear bodies. The prognostic significance of telomere maintenance mechanisms was analyzed by Cox regression in the overall series and in a subset of 29 patients who underwent a uniform treatment regimen consisting of cytoreductive surgery and hyperthermic i.p. chemotherapy.
  
  
  RESULTS
  Telomere maintenance mechanisms were detectable in 86.4% of DMPM: ALT or TA alone was found in 18.2% or 63.6% of lesions, respectively, whereas two cases (4.6%) were ALT+/TA+. TA and ALT proved to be inversely associated (P = 0.002). In the overall series, TA was prognostic for 4-year relapse (TA+ versus TA-, hazard ratio, 3.30; 95% confidence interval, 1.23-8.86; P = 0.018) and cancer-related death (TA+ versus TA-, hazard ratio, 3.56; 95% confidence interval, 1.03-12.51; P = 0.045), whereas ALT failed to significantly affect clinical outcome. These results held true also in the subset of patients submitted to uniform treatment with cytoreductive surgery and hyperthermic i.p. chemotherapy.
  
  
  CONCLUSIONS
  Our results indicate that both known telomere maintenance mechanisms, TA and ALT, are present in DMPM and differentially affect patient prognosis.
authors.affiliation: Department of Experimental Oncology and Surgery, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Villa
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.forename: Rosita
authors.initials: R
authors.lastname: Motta
authors.forename: Lorenza
authors.initials: L
authors.lastname: Venturini
authors.forename: Cinzia
authors.initials: C
authors.lastname: De Marco
authors.forename: Alberto
authors.initials: A
authors.lastname: Vannelli
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kusamura
authors.forename: Dario
authors.initials: D
authors.lastname: Baratti
authors.forename: Marcello
authors.initials: M
authors.lastname: Deraco
authors.forename: Aurora
authors.initials: A
authors.lastname: Costa
authors.forename: Roger R
authors.initials: RR
authors.lastname: Reddel
authors.forename: Nadia
authors.initials: N
authors.lastname: Zaffaroni
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D008954:Models, Biological; D010997:Pleural Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000648:ultrastructure*; D016896:Treatment Outcome
chemical_list: D019098:Telomerase