Molecular Landscape of ERBB2 Alterations in 14,956 Solid Tumors
Hao Wang, Ji Miao, Yazhou Wen, Xihua Xia, Yanan Chen, Mengli Huang, Shiqing Chen, Zhengyi Zhao, Yuzi Zhang, Chunzhu Chen, Xinhua Zhu
Abstract
ERBB2 abnormalities frequently occur and serve as rationale therapeutic targets in cancer. In this study, clinical and next-generation sequencing data from 14,956 patients across more than 20 tumor types were collected. A total of 406 (2.7%) patients were identified with ERBB2 amplifications, and 303 (2.0%) patients with pathogenic somatic ERBB2 mutations. ERBB2 amplifications fell most frequently in breast (15.9%) and stomach (8.3%) cancers. Somatic ERBB2 SNVs/indels occurred most common in bladder/urinary tract (7.3%) and intestine (6.1%) cancers. The top mutated ERBB2 SNVs/indels were p.Y772_A775dup (25.5%) and p.S310F/Y (19.9%). Significantly higher rates of ERBB2 SNV/indels were found in women compared to men (2.8% vs. 1.5%, p < 0.0001). CDK12 was the most common co-amplification gene with ERBB2 in cancers with a high frequency of ERBB2 amplifications. Patients with ERBB2 amplifications or mutations had higher TMB compared with patients with non- ERBB2 alterations. The study provided the landscape of ERBB2 alterations across a variety of solid tumors that may benefit from anti-HER2 agents.