# The Mutation Patterns of MET Gene in Lung Cancer and Brain Tumors: Clinical and Therapeutic Implications

## TL;DR

This study compares MET gene mutations in lung cancer and brain tumors, showing they have different clinical impacts and implications for treatment.

## Contribution

The study provides the first systematic comparison of MET mutation patterns and their clinical significance in lung cancer and brain tumors.

## Key findings

- Lung cancer has a higher overall frequency of MET mutations compared to brain tumors.
- MET alterations are associated with poorer survival in brain tumors but not in lung cancer.
- MET mutations in brain tumors are more common in post-treated patients and correlate with genomic instability.

## Abstract

MET
aberrations are capable of triggering oncogenesis through multiple clinical significance genomic alterations. In non‐small cell lung cancer,
MET
exon 14 skipping and
MET
amplification confer sensitivity to MET tyrosine kinase inhibitors. The
MET
gene is also one of the druggable genes in high‐grade gliomas. However, a systematic comparison of
MET
variations between lung cancer and brain tumors is lacking.

We analyzed a large Chinese cohort of 30,355 lung cancer and 6004 brain tumor patients. Different MET mutation types were characterized, and somatic genomic mutational characteristics were examined across various MET mutation subgroups in both lung cancer and brain tumor cohorts. The impact of MET mutations on prognosis in these two cohorts was also assessed. The study cohort underwent comprehensive genomic profiling using targeted next‐generation sequencing (NGS) panels.

We found that clinically significant MET mutations exist in both lung and brain tumor cohorts, with the lung cancer group having a higher overall frequency (p < 0.001), but the frequency of different MET mutation types, mutation characteristics, tumor mutation burden, and co‐mutated genes with high frequency all differ. MET alterations were significantly enriched in post‐treatment brain tumors (8.5% vs. 4.8% in treatment‐naïve, p < 0.001). MET mutations also have different prognostic effects in the two cancer types. MET alterations were not prognostic in lung cancer but were associated with significantly poorer survival in brain tumors (median OS: 19.9 vs. 62.9 months, p < 0.001), a finding that held in multivariate analysis.

Our study demonstrated that the biological and clinical significance of MET alterations is highly context dependent. In lung cancer, MET serves primarily as a predictive biomarker for targeted therapy, whereas in brain tumors, it functions as a prognostic marker of genomic instability and aggressive disease. These findings advocate for context‐specific clinical management strategies.