Hong Lingzhi, Patel Sonia, Drusbosky Leylah M, Xiong Yuanyuan, Chen Rongrong, Geng Ruixuan, Heeke Simon, Nilsson Monique, Wu Jia, Heymach John V, Wang Yingyi, Zhang Jianjun, Le Xiuning
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
NPJ Precis Oncol. 2024 Oct 1;8(1):217. doi: 10.1038/s41698-024-00720-9.
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.
ERBB2（HER2）是一种新发现的可作用于非小细胞肺癌（NSCLC）的致癌驱动因子，已有获批的靶向治疗药物。了解ERBB2改变和共发突变的情况对于指导治疗决策至关重要。我们对3000例患有各种ERBB2改变的NSCLC患者进行了分析，这些患者来自两个广泛的回顾性队列：1281例来自Geneplus（中国），1719例来自Guardant360（美国）。在中国组中，所有类型的ERBB2改变的发生率为5.6%，在美国组中为5.2%。在两个队列中，在ERBB2的致癌改变中，外显子20插入Y772_A775dupYVMA是最常见的改变（中国组为58%，美国组为41.6%），其次是G776delinsVC/LC/VV/IC（10.7%对9.7%）和S310X（10.5%对15.4%）。在A767 - V774区域鉴定出EGFR外显子20插入，而在Y772 - P780区域观察到ERBB2外显子20插入。值得注意的是，EGFR外显子20插入表现出更大的插入多样性。EGFR和ERBB2外显子20 NSCLC的临床特征相似，表现为低肿瘤突变负荷（TMB）、以从不吸烟者为主的人群以及大多数肺腺癌病例。
