AUTHOR=Wang Hao , Miao Ji , Wen Yazhou , Xia Xihua , Chen Yanan , Huang Mengli , Chen Shiqing , Zhao Zhengyi , Zhang Yuzi , Chen Chunzhu , Zhu Xinhua 

TITLE=Molecular Landscape of ERBB2 Alterations in 14,956 Solid Tumors

JOURNAL=Pathology and Oncology Research

VOLUME=28

YEAR=2022

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2022.1610360

DOI=10.3389/pore.2022.1610360

ISSN=1532-2807

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