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. 2022 Jul 13:28:1610360.
doi: 10.3389/pore.2022.1610360. eCollection 2022.

Molecular Landscape of ERBB2 Alterations in 14,956 Solid Tumors

Hao Wang  1 , Ji Miao  1 , Yazhou Wen  2 , Xihua Xia  3 , Yanan Chen  3 , Mengli Huang  3 , Shiqing Chen  3 , Zhengyi Zhao  3 , Yuzi Zhang  3 , Chunzhu Chen  3 , Xinhua Zhu  1
Affiliations

Molecular Landscape of ERBB2 Alterations in 14,956 Solid Tumors

Hao Wang et al. Pathol Oncol Res. .

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.

Keywords: ERBB2; TMB; anti-HER2 agents; next-generation sequencing; solid tumors.

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Conflict of interest statement

XX, YC, MH, SC, ZZ, YZ, and CC were employed by 3D Medicines Inc. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Landscape of ERBB2 alterations. (A) Landscape of ERBB2 amplifications and ERBB2 mutations across different tumor types. (B) Prevalence of the pathogenic or very likely pathogenic somatic mutations of ERBB2 in furin-like region, transmembrane domain, and tyrosine kinase domain. (C) ERBB2 somatic mutation map.
FIGURE 2
FIGURE 2
Top 20 high-frequency mutated genes in ERBB2-mutated patients of bladder/urinary tract cancer (A), intestine cancer (B), stomach cancer (C), lung cancer (D), kinase domain, and non-kinase domain in lung cancer (E).
FIGURE 3
FIGURE 3
Top 20 high-frequency mutated genes in ERBB2-amplification patients of breast cancer (A), stomach cancer (B), biliary tract cancer (C), colorectal cancer (D), and co-amplification genes accompanying ERBB2 amplification in breast cancer (E), stomach cancer (F), biliary tract cancer (G), colorectal cancer (H).
FIGURE 4
FIGURE 4
Association between ERBB2 alterations and TMB. (A) Comparison of TMB in patients with ERBB2-amplification and non-ERBB2-amplification. (B) Comparison of TMB in all patients with ERBB2-mutation and non-ERBB2-mutation and in bladder/urinary tract cancer (C), stomach cancer (D), colorectal cancer (E), lung cancer (F).
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