Mutational landscape and characteristics of ERBB2 in non‐small cell lung cancer

作者：Xue‐Wu Wei, Xin Gao, Xu‐Chao Zhang, Jin‐Ji Yang, Zhihong Chen, Yi‐Long Wu, Qing Zhou · 发表于：Thoracic Cancer · 年份：2020 · DOI：10.1111/1759-7714.13419 · 被引用次数：65 · 研究领域：Lung Cancer Treatments and Mutations、Melanoma and MAPK Pathways、Lung Cancer Diagnosis and Treatment

BACKGROUND: Tyrosine kinase domain (TKD) mutation and particularly exon 20 insertion mutations of ERBB2 have been extensively reported in non-small cell lung cancer (NSCLC). Due to the increased accessibility of next-generation sequencing, more ERBB2 mutations within the non-TKD can be detected in clinical practice. Nevertheless, the clinical significance of non-TKD mutations remains unknown. Hence, this study was designed to comprehensively outline the landscape and characteristics of ERBB2 mutations in NSCLC. METHODS: A total of 1934 patients with NSCLC from cBioPortal were included in the study. An ERBB2 mutation cohort was identified, while subsequent analyses revealed clinical and genomic characteristics. RESULTS: The frequency of ERBB2 mutation was 4.5%, and it was determined to be more likely to occur in never-smokers. ERBB2 mutations occurring in the non-TKD accounted for 57.5% of ERBB2 mutations. In the non-TKD, missense mutation was the most recurrent mutation type, and S310F was the most recurrent mutation variant. ERBB2 mutations within non-TKD also had a strong oncogenic ability where up to 37.5% of ERBB2 oncogenic mutations were within non-TKD. The co-mutation of EGFR or KRAS was higher in the non-TKD mutation compared to the TKD mutation. Shorter overall survival was observed in ERBB2-mutant patients compared with ERBB2 wild-type patients. There was no significant difference in overall survival between patients with non-TKD mutations and TKD mutations. CONCLUSI...