Abstract

ERBB2 (HER2) represents a newly recognized actionable oncogenic driver in non-small cell lung cancer (NSCLC), with approved targeted therapy available. Understanding the landscape of ERBB2 alterations and co-occurring mutations is essential for guiding treatment decisions. We conducted an analysis involving 3000 NSCLC patients with all types of ERBB2 alterations, drawn from two extensive retrospective cohorts: 1281 from Geneplus (Chinese) and 1719 from Guardant360 (the United States, US). The incidence of all types of ERBB2 alterations was found to be 5.6% in the Chinese group and 5.2% in the US group. In both cohorts, among oncogenic alterations of ERBB2, exon 20 insertion Y772_A775dupYVMA was the most frequent alteration (58% vs 41.6% in the Chinese vs the US), followed by G776delinsVC/LC/VV/IC (10.7% vs 9.7%), and S310X (10.5% vs 15.4%). EGFR ex20 insertions were identified in the A767-V774 region, whereas ERBB2 ex20 insertions were observed in the Y772-P780 region. Notably, EGFR ex20 insertions exhibited greater insertion diversity. Clinical characteristics of EGFR and ERBB2 ex20 NSCLC were similar, characterized by low tumor mutation burden (TMB), a predominant never-smoker population, and a majority of lung adenocarcinoma cases.

Details

Title
Molecular landscape of ERBB2 alterations in 3000 advanced NSCLC patients
Author
Hong, Lingzhi 1   VIAFID ORCID Logo  ; Patel, Sonia 2 ; Drusbosky, Leylah M. 3 ; Xiong, Yuanyuan 4 ; Chen, Rongrong 4 ; Geng, Ruixuan 5 ; Heeke, Simon 2   VIAFID ORCID Logo  ; Nilsson, Monique 2 ; Wu, Jia 1   VIAFID ORCID Logo  ; Heymach, John V. 2   VIAFID ORCID Logo  ; Wang, Yingyi 6 ; Zhang, Jianjun 7   VIAFID ORCID Logo  ; Le, Xiuning 2   VIAFID ORCID Logo 

 The University of Texas MD Anderson Cancer Center, Department of Thoracic/Head and Neck Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center, Department of Imaging Physics, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
 The University of Texas MD Anderson Cancer Center, Department of Thoracic/Head and Neck Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
 Guardant Health, Redwood City, USA (GRID:grid.511203.4) 
 Geneplus-Beijing, Beijing, China (GRID:grid.512993.5) 
 Chinese Academy of Medical Sciences and Peking Union Medical College, Department of International Medical Services, Peking Union Medical College Hospital, Beijing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839) 
 Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Medical Oncology, Peking Union Medical College Hospital, Beijing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839) 
 The University of Texas MD Anderson Cancer Center, Department of Thoracic/Head and Neck Medical Oncology, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776); The University of Texas MD Anderson Cancer Center, Department of Genomic Medicine, Houston, USA (GRID:grid.240145.6) (ISNI:0000 0001 2291 4776) 
Pages
217
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
ISSN
2397768X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3111725701
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.