title: MYC and human telomerase gene (TERC) copy number gain in early-stage non-small cell lung cancer.
abstract: OBJECTIVE
  We investigated the frequency of MYC and TERC increased gene copy number (GCN) in early-stage non-small cell lung cancer (NSCLC) and evaluated the correlation of these genomic imbalances with clinicopathologic parameters and outcome.
  
  
  METHODS
  Tumor tissues were obtained from 113 resected NSCLCs. MYC and TERC GCNs were tested by fluorescence in situ hybridization (FISH) according to the University of Colorado Cancer Center (UCCC) criteria and based on the receiver operating characteristic (ROC) classification.
  
  
  RESULTS
  When UCCC criteria were applied, 41 (36%) cases for MYC and 41 (36%) cases for TERC were considered FISH-positive. MYC and TERC concurrent FISH-positive was observed in 12 cases (11%): 2 (17%) cases with gene amplification and 10 (83%) with high polysomy. By using the ROC analysis, high MYC (mean ≥ 2.83 copies/cell) and TERC (mean ≥ 2.65 copies/cell) GCNs were observed in 60 (53.1%) cases and 58 (51.3%) cases, respectively. High TERC GCN was associated with squamous cell carcinoma (SCC) histology (P=0.001). In univariate analysis, increased MYC GCN was associated with shorter overall survival (P=0.032 [UCCC criteria] or P=0.02 [ROC classification]), whereas high TERC GCN showed no association. In multivariate analysis including stage and age, high MYC GCN remained significantly associated with worse overall survival using both the UCCC criteria (P=0.02) and the ROC classification (P=0.008).
  
  
  CONCLUSIONS
  Our results confirm MYC as frequently amplified in early-stage NSCLC and increased MYC GCN as a strong predictor of worse survival. Increased TERC GCN does not have prognostic impact but has strong association with squamous histology.
authors: *Department of Medical Oncology, S. Maria della Misericordia Hospital Departments of †Electronic and Information Engineering ‡Thoracic Surgery §Institute of Pathological Anatomy and Histology, University of Perugia, Perugia, Italy ∥Department of Medicine/Medical Oncology, University of Colorado Cancer Center, Aurora, CO.
authors: Antonella
authors: A
authors: Flacco
authors: Vienna
authors: V
authors: Ludovini
authors: Fortunato
authors: F
authors: Bianconi
authors: Mark
authors: M
authors: Ragusa
authors: Guido
authors: G
authors: Bellezza
authors: Francesca R
authors: FR
authors: Tofanetti
authors: Lorenza
authors: L
authors: Pistola
authors: Annamaria
authors: A
authors: Siggillino
authors: Jacopo
authors: J
authors: Vannucci
authors: Lucio
authors: L
authors: Cagini
authors: Angelo
authors: A
authors: Sidoni
authors: Francesco
authors: F
authors: Puma
authors: Marileila
authors: M
authors: Varella-Garcia
authors: Lucio
authors: L
authors: Crinò
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D018628:Gene Dosage; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012313:RNA / Q000235:genetics*; D012372:ROC Curve; D012189:Retrospective Studies; D019098:Telomerase / Q000235:genetics*
chemical_list: C422952:telomerase RNA; D012313:RNA; D019098:Telomerase