MYC and human telomerase gene (TERC) gene copy number gain in resected in non-small cell lung cancer (NSCLC).

Abstract

10580 Background: Long-term survival of resected NSCLC is disappointing and targets for a new generation of therapeutic agents are necessary. Abnormalities in MYC are well known in lung cancer and TERC maps in chromosomal region with frequent copy number gain (CNG) in NSCLC. This study investigates the incidence of MYC and TERC CNG and evaluates their correlation with clinicopathological parameters and outcome in resected NSCLC. Methods: 113 NSCLC patients subjected to curative pulmonary resection were tested for TERC and MYC CNG by fluorescence in situ hybridization (FISH) using commercial probes. Median age was 66 years (range 40–84); most patients were male (84%), former/current smokers (92%), had poorly differentiated histology (42%) and stage I disease (62%). The histological types included 51% squamous cell carcinoma (SCC), 30% adenocarcinoma, 8% BAC, and 11% of other subtypes. CNG was determined when ≥4 gene copies were displayed in ≥40% of tumor cells. Kaplan-Meier estimates of survival and time to recurrence were calculated for clinical variables and biologic markers using the Cox model for multivariate analysis. Results: Forty-one (36%) patients showed CNG for MYC and 41 (36%) for TERC. MYC and TERC gene amplification (GA) were found in 9 (8%) and 15 (13%) cases, respectively. MYC and TERC contemporary CNG was observed in 12 cases (11%): 2 (17%) cases with GA vs 10 (83%) high polysomy. TERC CNG was associated with SCC histology (80% vs 20% in non-SCC; p=0.001). In univariate analyses, both MYC CNG and GA were associated with shorter disease free survival (DFS, p=0.032 and P=0.022, respectively) and overall survival (OS; p<0.032 and P<0.000, respectively) while TERC CNG or GA showed no association. In multivariate analysis including stage and age, MYC CNG and GA remained significantly associated with worse DFS (p=0.022; p= 0.011 respectively) and OS (p=0.026; p<0.000), respectively). Conclusions: Our results indicate that MYC and TERC are frequently amplified in NSCLC. TERC CNG shows phenotypic properties strongly associated with SCC and is not a prognostic factor. CNG for MYC is a strong predictor of worse survival. We thank the Italian Association for Cancer Research AIRC (AF Fellowship).