HER2 transmembrane domain mutation: comprehensive characteristics and real-world evidence of treatment response in Chinese lung adenocarcinoma

transmembrane domain (TMD) mutation has been reported as a rare driver mutation associated with advanced stage disease and a poor prognosis in patients with lung adenocarcinoma (LUAD). We aimed to comprehensively profile the genetic landscape and treatment response information of TMD-mutant LUAD. An in-house database of 7,812 LUAD patients was screened for mutation prevalence. A multi-center cohort of 16 V659E-mutant patients and an external cohort of 38 -mutant patients from cBioPortal with overall survival (OS) data were analyzed. Eight patients from the in-house cohort were included in the real-world study of treatment response. Molecular docking simulation and binding affinity prediction were performed. In Chinese LUAD, the prevalence of TMD mutation was 0.18% (14/7,812), and 0.14% (11/7,812) for the V659E mutation. The most recurrent co-alteration was mutation (n=4, 25%) and amplification (n=2, 12.5%). TMD-mutant patients were diagnosed at more advance stages (P