OA02 Targeted Next-Generation Sequencing Reveals Relapse-Associated Genomic Alterations in Early Stage Non-Small Cell Lung Cancer

Although early stage non-small cell lung cancer (NSCLC) patients have better prognosis than advanced stage patients, there is a relatively high rate of recurrence and individual variations. The identification of genomic alterations related to recurrence may help better stratify high-risk individuals and guide treatment strategies. This study aimed to identify the molecular biomarkers of recurrence in early stage NSCLC. Paired primary tumor and normal lung tissue samples were collected for targeted next-generation sequencing analysis. A targeted panel targets exons for 440 genes was used to assess the mutational and copy number status of selected genes in three clinically relevant groups of stage I/II NSCLC patients: 1) Early relapse; 2) Late relapse; and 3) No relapse. Of the 42 tumors evaluable for genomic alterations, TP53 and EGFR were the most frequent alterations with population frequency 52.4% and 50.0%, respectively. Fusion genes were detected in four patients, which had lower mutational burden and relatively better genomic stability. EGFR mutation and fusion gene were mutually exclusive in this study. CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were only observed in the relapsed patients. Tumor mutational burden and copy number alteration (CNA) index didn’t show significant differences in each group. Increased CNA index was observed in early relapsed patients. Among these genomic alterations, early-stage NSCLCs harboring CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were found to be significantly associated with recurrence. Some of these findings were validated in The Cancer Genome Atlas dataset. The genomic alterations of CDKN2A, FAS, SUFU and SMARCA4 in early stage NSCLC may be potential biomarkers of recurrence, but confirmation in a larger independent cohort is required to define the clinical value.