In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 8546-8546
Abstract:
8546 Background: Activating mutations in the ERBB2 gene were shown to play an oncogenic role similar to that of ERBB2 amplification. Thus, ERBB2 mutations have emerged as therapeutic targets in non-small cell lung cancers (NSCLC). However, Activating ERBB2 mutations have not been described in detail like other driver gene mutations, such as epidermal growth factor receptor (EGFR)-activating mutations. Methods: In this study, we retrospectively analyzed activating ERBB2 mutations using next-generation sequencing(NGS). From May 2019 to January 2022, 21745 patients who were diagnosed with NSCLC were detected. Results: A total of 686 activating ERBB2 mutations were found, and 12 patients carried double ERBB2-activating mutations. In this cohort, the average age of patients was 58 years (range, 13-90 years). 59.6% of the patients were female and 88.2% were diagnosed with lung adenocarcinoma.A total of 47 ERBB2-activating mutation subtypes were defined in 674 patients. The most common activating mutations were Y772_A775dup (55.0%, 371/674), followed by G776delinsVC (8.3%, 56/674), S310F (7.7%, 52/674), G778_P780dup (5.6%, 38/674) and V659E (4.1%, 28/674). All other mutations occurred in 14 or fewer patients. ERBB2-activating mutations occurred most frequently in the tyrosine kinase domain(TKD) (80.1%), which included mutations in exon 20 (76.2%), exon 19 (3.0%), and exon 21 (1.2%),In addition, 13.2% of activating ERBB2 mutations occur in the extracellular domain, and 5.5% in the Transmembrane domain. 23.1%(156/674) patients with ERBB2 activating mutations could be evaluated for concurrent mutations, tumor mutational burden (TMB) and microsatellite instability (MSI) status. Among these patients, ERBB2-activating mutations were most frequently co-mutated with TP53(54/156) and EGFR(21/156). The frequency of EGFR mutations was much higher in non-TKD mutation patients than in TKD mutation patients (56.7% vs. 3.2%, P 〈 0.001), but no difference was observed for TP53. All these patients were microsatellite stable (MSS) and low TMB ( 〈 10 mutations/megabase). Conclusions: We report mutational landscape and characteristics of ERBB2 in Chinese NSCLC patients.The prevalence of activating ERBB2 mutations was 3.1% in Chinese NSCLC patients. 80.1% of ERBB2 activating mutations were in TKD and 19.9% were in the non-TKD. The non-TKD mutations might also be used as a therapeutic target in ERBB2-directed target therapy.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2022.40.16_suppl.8546
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2022
detail.hit.zdb_id:
2005181-5
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