MET Exon 2 Skipping Mutation Associated With Self-Regulatory Mechanism for Advanced NSCLC
Key Clinical Summary
- Design/Population: At the 2025 Association for Molecular Pathology Annual Meeting & Expo, a retrospective analysis evaluated 111 patients with NSCLC harboring MET exon 2 skipping mutations (mean age 69.95 years; 56% male). Most cases were adenocarcinoma (77.4%), and 97.3% presented with stage III/IV disease; 92.8% were metastatic at diagnosis.
- Key Outcomes: High mutation burden and frequent co-occurring driver mutations (74.8%) were observed—most commonly KRAS (n=45), EGFR (n=23), and BRAF (n=11). Median overall survival was 335.7 days, with 63.9% mortality within 3 years.
- Clinical Relevance: Findings link MET exon 2 skipping to aggressive, late-stage NSCLC biology and frequent oncogenic co-mutations, suggesting a need for further molecular characterization to clarify therapeutic and prognostic implications.
Results from a retrospective analysis analyzing patients with non-small cell lung cancer (NSCLC) cases harboring MET exon 2 skipping mutations found that these mutations were associated with a threshold for a self-regulatory mechanism, according to study results from the 2025 Association for Molecular Pathology Annual Meeting & Expo.
Research is limited on the clinical behavior of tumors with MET exon 2 skipping mutations, though the biological role has been researched and documented. To address this need, researchers conducted a retrospective analysis to determine the clinical role of MET exon 2 skipping mutations.
Overall, 111 patients were included in the analysis, of which 62 were male and 49 were female and the mean age was 69.95 years. Most tumors were adenocarcinomas (77.4%), with smaller proportions of squamous cell carcinoma (11.7%).
A majority of patients had a smoking history (87.4%), and 92.8% presented with metastatic disease. Nearly all cases were stage III/IV at diagnosis (97.3%), and 63.9% of patients died within 3 years, with a mean overall survival of 335.7 days following diagnosis.
Co-occurring tier 1/2 driver mutations were identified among 74.8% of patients which included, KRAS (n=45), EGFR (n=23), and BRAF (n=11). Additional concurrent alterations were found in TP53 (n=9), NRAS (n=5), ERBB2 (n=4), STK11 (n=3), RET (n=2), ALK (n=1), and
The researchers concluded, MET exon 2’s “skipping results in a Met mRNA that fails protein translation and hence were documented as a post-transcriptional self-regulatory mechanism by tumor cells to limit Met receptor expression.”
“Our findings on its association with advanced stage NSCLC are striking, indicating presence of a threshold at which tumor cells activate the self-regulatory mechanism to rein in their cancerous growth and to avoid triggering apoptotic process,” they added.
Source:
Bava EP, Aldilaimi A, Abbas O, et al. MET Exon 2 Skipping Mutation and Its Implications in Advanced Stage Non-Small Cell Lung Carcinomas. Presented at the 2025 AMP Annual Meeting. November 11-15, 2025; Boston, Massachusetts. ST180
