TY - JOUR AU - Rotolo, Federico AU - Zhu, Chang-Qi AU - Brambilla, Elisabeth AU - Graziano, Stephen L. AU - Olaussen, Ken AU - Le-Chevalier, Thierry AU - Pignon, Jean-Pierre AU - Kratzke, Robert AU - Soria, Jean-Charles AU - Shepherd, Frances A. AU - Seymour, Lesley AU - Michiels, Stefan AU - Tsao, Ming-Sound AU - LACE-Bio Consortium, on behalf of the PY - 2018 TI - Genome-wide copy number analyses of samples from LACE-Bio project identify novel prognostic and predictive markers in early stage non-small cell lung cancer JF - Translational Lung Cancer Research; Vol 7, No 3 (June 14, 2018): Translational Lung Cancer Research (Lung Cancer Screening) Y2 - 2018 KW - N2 - Background: Adjuvant chemotherapy (ACT) provides modest benefit in resected non-small cell lung cancer (NSCLC) patients. Genome-wide studies have identified gene copy number aberrations (CNA), but their prognostic implication is unknown. Methods: DNA from 1,013 FFPE tumor samples from three pivotal multicenter randomized trials (ACT vs . control) in the LACE-Bio consortium (median follow-up: 5.2 years) was successfully extracted, profiled using a molecular inversion probe SNP assay, normalized relative to a pool of normal tissues and segmented. Minimally recurrent regions were identified. P values were adjusted to control the false discovery rate (Q values). Results: A total of 976 samples successfully profiled, 414 (42%) adenocarcinoma (ADC), 430 (44%) squamous cell carcinoma (SCC) and 132 (14%) other NSCLC; 710 (73%) males. We identified 431 recurrent regions, with on average 51 gains and 43 losses; 253 regions (59%) were ≤3 Mb. Most frequent gains (up to 48%) were on chr1, 3q, 5p, 6p, 8q, 22q; most frequent losses (up to 40%) on chr3p, 8p, 9p. CNA frequency of 195 regions was significantly different (Q≤0.05) between ADC and SCC. Fourteen regions (7p11–12, 9p21, 18q12, and 19p11–13) were associated with disease-free survival (DFS) (univariate P≤0.005, Q CDKN2A/B [hazard ratio (HR) for 2-fold lower CN: 1.5 (95% CI: 1.2–1.9), P Conclusions: These large-scale genome-wide analyses of gene CNA provide new candidate prognostic markers for stage I–III NSCLC. UR - https://tlcr.amegroups.org/article/view/21273