MET alterations are enriched in lung adenocarcinoma brain metastases, defining a distinct biologic subtype.

ABSTRACT: Non-small cell lung cancer exhibits the highest rates of brain metastases (BMs) among all solid tumors, presenting a major clinical challenge. The development of novel therapeutic strategies targeting BMs is clearly needed. We identified a significant enrichment of MET amplification in lung adenocarcinoma (LUAD) BMs compared with primary LUAD and extracranial metastases in oncogene driver-negative patients. Of note, MET-amplified BMs were responsive to MET inhibitors in vivo, including models with acquired MET amplification at the time of metastasis. MET alterations (amplifications and/or mutations) were also more frequently detected in circulating tumor DNA from patients with LUAD BMs than in those without BMs. MET-altered BMs also demonstrated unique genomic features compared with non-ME

SUBMITTER: Burns TF 

PROVIDER: S-EPMC12904726 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature