Wide Next-Generation Sequencing Characterization of Young Adults Non-Small-Cell Lung Cancer Patients

Simple Summary Molecular characterization of advanced non-small-cell lung cancer (NSCLC) is mandatory before any treatment decision making. Next-generation sequencing (NGS) approaches represent the best strategy in this context. In our study, we analyzed a case series of young (under 65 years old) NSCLC patients with a wide NGS gene panel assay. The most frequent altered genes were TP53 (64.55%), followed by KRAS (44.1%), STK11 (26.9%), CDKN2A (21.5%), CDKN2B (14.0%), EGFR (16.1%), and RB1 (10.8%). Tumor mutational burden (TMB) was also evaluated considering different cut-offs, and we found a significant association between TMB and STK11 and KRAS mutations. Conversely, EGFR and EML4-ALK alterations were more frequently found in tumors with low TMB. We compared results obtained from this approach with those obtained from a single or few genes approach, observing perfect concordance of the results. Molecular characterization of advanced non-small-cell lung cancer (NSCLC) is mandatory before any treatment decision making. Next-generation sequencing (NGS) approaches represent the best strategy in this context. The turnaround time for NGS methodologies and the related costs are becoming more and more adaptable for their use in clinical practice. In our study, we analyzed a case series of young (under 65 years old) NSCLC patients with a wide NGS gene panel assay. The most frequent altered genes were TP53 (64.55%), followed by KRAS (44.1%), STK11 (26.9%), CDKN2A (21.5%), CDKN2B (14.0%), EGFR (16.1%), and RB1 (10.8%). Tumor mutational burden (TMB) was also evaluated. Considering the cut-off of 10 mut/Mb, 62 (68.9%) patients showed a TMB < 10 mut/Mb, whereas 28 (31.1%) showed a TMB >= 10 mut/Mb. STK11 and KRAS mutations were significantly associated with a higher TMB (p = 0.019 and p = 0.004, respectively). Conversely, EGFR and EML4-ALK alterations were more frequently found in tumors with low TMB (p = 0.019 and p < 0.001, respectively). We compared results obtained from this approach with those obtained from a single or few genes approach, observing perfect concordance of the results.

Automated summary

Molecular characterization of advanced non-small-cell lung cancer (NSCLC) is essential for treatment decision making, and next-generation sequencing (NGS) is the best strategy in this context. In this study, we analyzed a series of young NSCLC patients using a wide NGS gene panel assay. The most frequently mutated genes were TP53, KRAS, STK11, etc. We found a significant association between STK11 and KRAS mutations and high tumor mutational burden (TMB), while EGFR and EML4-ALK alterations were more common in tumors with low TMB. The results obtained from this approach showed perfect concordance with those obtained from a single or few genes approach.