Molecular Landscape of ERBB2 Alterations in 14,956 Solid Tumors

Abstract

<i>ERBB2</i> 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 <i>ERBB2</i> amplifications, and 303 (2.0%) patients with pathogenic somatic <i>ERBB2</i> mutations. <i>ERBB2</i> amplifications fell most frequently in breast (15.9%) and stomach (8.3%) cancers. Somatic <i>ERBB2</i> SNVs/indels occurred most common in bladder/urinary tract (7.3%) and intestine (6.1%) cancers. The top mutated <i>ERBB2</i> SNVs/indels were p.Y772_A775dup (25.5%) and p.S310F/Y (19.9%). Significantly higher rates of <i>ERBB2</i> SNV/indels were found in women compared to men (2.8% vs. 1.5%, <i>p</i> < 0.0001). <i>CDK12</i> was the most common co-amplification gene with <i>ERBB2</i> in cancers with a high frequency of <i>ERBB2</i> amplifications. Patients with <i>ERBB2</i> amplifications or mutations had higher TMB compared with patients with non-<i>ERBB2</i> alterations. The study provided the landscape of <i>ERBB2</i> alterations across a variety of solid tumors that may benefit from anti-HER2 agents.