Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer

• Published in: Oncotarget Vol. 9; no. 91; pp. 36344 - 36357
• Main Authors: Cho, William C S, Tan, Kien Thiam, Ma, Victor W S, Li, Jacky Y C, Ngan, Roger K C, Cheuk, Wah, Yip, Timothy T C, Yang, Yi-Ting, Chen, Shu-Jen
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 20.11.2018
• Subjects: Research Paper; lung cancer; early-stage; biomarker; next-generation sequencing; relapse
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.26349

The identification of genomic alterations related to recurrence in early-stage non-small cell lung cancer (NSCLC) patients 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. 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. Increased copy number alteration 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 new findings were validated using The Cancer Genome Atlas (TCGA) dataset. The genomic alterations of CDKN2A, FAS, SUFU and SMARCA4 in early-stage NSCLC are found to be associated with recurrence, but confirmation in a larger independent cohort is required to define the clinical impact. Paired primary tumor and normal lung tissue samples were collected for targeted next-generation sequencing analysis. A 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.