A recent retrospective analysis identified clinically relevant subgroups of non–small cell lung cancer (NSCLC) adenocarcinoma with altered genetic profiles and reduced survival. The study, based on tissue-based next-generation sequencing (NGS), found that tumors with amplified HER2, KRAS, and MET genes exhibited decreased co-occurrence with oncogenic drivers as copy number gains increased. Tumors with these amplified genes were less likely to be driver-positive, and a negative association with overall survival was observed, particularly for HER2 and MET amplification. Amplified MET tumors showed higher hazard ratios for death compared to non-amplified tumors, regardless of the presence of oncogenic driver mutations.
The study’s findings highlight the potential of using NGS to define meaningful thresholds for copy number gain in NSCLC, rather than arbitrarily selecting thresholds. Using an oncogene overlap approach, the researchers determined that increasing copy number gains of HER2, KRAS, and MET were linked to a decreased frequency of co-occurring driver mutations. For example, HER2 amplification above a threshold of 6 copies led to a significant reduction in the presence of oncogenic driver mutations. The researchers suggest that further research is needed to explore the implications of these findings in targeted therapy trials, particularly for patients with amplified HER2, KRAS, and MET genes.
Reference: Hollasch M. Tissue-Based NGS May Help Determine Relevant Gene Copy Number Gain Cutpoint for HER2/KRAS/MET in NSCLC. OncLive. Published January 29, 2025. Accessed February 15, 2025. https://www.onclive.com/view/tissue-based-ngs-may-help-determine-relevant-gene-copy-number-gain-cutpoint-for-her2-kras-met-in-nsclc
