Clinical and molecular characteristics of Chinese non-small cell lung cancer patients with ERBB2 transmembrane domain mutations.

摘要: Transmembrane domain (TMD) mutations of ERBB2 have previously been reported in lung cancer patients addition to well-studied kinase (KD) mutations, which may stabilize heterodimerization with other EGFR family members and favor a active conformation. However, the frequency clinical significance TMD Chinese population is unknown. We prospectively analyzed next-generation sequencing data 34 368 different sample types, including tumor tissue, plasma, cerebrospinal fluid, pleural effusion. Patients' characteristics treatment history were retrieved from database for further evaluation. Our findings show that V659/G660 detected at 0.13% (45/34 368), most frequent was V659D/E (88.9%), trend nonsmokers male. Moreover, 18% (8/45) showed and/or amplification, whereas nine presented L858R or exon19 deletion. Interestingly, novel ERBB3 mutation I646R found coexisting three V659D one patient G660D, might influence its activate ERBB2. Four mutation-positive received afatinib monotherapy combination therapy, but variable responses. One V659E responded well inhibitor lapatinib plus capecitabine as subsequent upon progression. study provides valuable insights into distribution by employing largest Asian cohort thus far. Patients who afatinib, pan-ERBB inhibitor, demonstrated mixed responses, posing urgent need develop more effective therapeutic strategy carry mutations.