Abstract 4665: Real-world data of resected early-stage non-small cell lung cancer (NSCLC) harboring copy number variations

Abstract Introduction: Copy number variations (CNVs) in several genetic regions are associated with cancer susceptibility and poor clinical outcomes. Currently, the role of CNVs in Non-Small Cell Lung Cancer (NSCLC) is relatively vague. This study investigates the CNVs profile in early-stage NSCLC. Methods: We retrospectively analyzed the next-generation sequencing (NGS) data of tumor tissue specimens from NSCLC patients over the past 3 years in our center. All samples were obtained by surgical resection, and clinical characteristics were collected for further analysis. Results: A total of 102 early-stage NSCLC performed NGS in our study, the mean age was 60.5 years, with 51% female. Genomic analysis revealed that 85.3% (87/102) patients had driver gene mutations, predominantly EGFR mutations (72/102) and ALK fusions (6/102). CNVs were observed in 29 NSCLC patients, including 22 with EGFR mutations, 1 with ALK fusion, 1 with BRAF V600E, and 5 without driver gene mutations. Among patients with CNVs, 9p21 (CDKN2A/CDKN2B) copy number losses were most frequent (24.1%, 7/29), followed by EGFR copy number gains (20.7%, 6/29), MYC copy number gains (13.8%, 4/29), and GATA1 copy number losses (13.8%, 4/29). There was no significant difference in age (median: 63 vs 61 years, P=0.504, Mann-Whitney U test) and sex (male: 66% vs 34%, P=0.221, chi-square test) between patients with and without CNVs. A significant trend of increased CNVs was observed in smokers compared to non-smokers (CNVs: 45.5% vs. 23.8%, P=0.046, chi-square test). Patients with small tumors accompanied by lymph node metastasis showed a significantly higher incidence of driver gene fusions than those without lymph node metastasis (T1-2N1-2 vs. T1-2N0 = 50.0% vs. 7.7%, P<0.001, chi-square test). However, no significant difference in CNVs incidence was found between these groups. The prognostic value of CNVs requires further validation through follow-up. Conclusions: Our study reveals a high prevalence of copy number losses of 9p21 (CDKN2A/CDKN2B) exists in early-stage non-small cell lung cancer. And we find that NSCLC patients with a history of smoking are more likely to have copy number variations. Citation Format: Jun Wang, Ning Gao, Ding Zhang. Real-world data of resected early-stage non-small cell lung cancer (NSCLC) harboring copy number variations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4665.