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Updated: Sep 30, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Clinicopathologic and molecular characteristics of Chinese lung adenocarcinoma patients with EGFR exon 20 insertion
Lifeng Wang1, Zichen Liu2, Zhiyi Wan3
1Department of Pathology, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, China.
Background:
Epidermal growth factor receptor exon 20 insertions (EGFR ex20ins) occur in about 4-14% of lung adenocarcinoma (LUAD) patients with EGFR mutations. Recently some targeted drugs have been approved for the treatment of LUAD patients with EGFR ex20ins. However, the heterogeneity of EGFR ex20ins mutations and resultant challenges in identifying them have led to the underestimation of their frequency.
Methods:
We investigated the molecular and clinicopathologic features of EGFR ex20ins in 3,892 Chinese LUAD patients using next-generation sequencing (NGS). The frequency and distribution of EGFR ex20ins mutations between Chinese and Western LUAD patients were also compared by integrating the data of this study and the data of previous studies.
Results:
A total of 23 unique EGFR ex20ins were identified in 77 LUAD patients, accounting for 1.98% of all LUAD patients and 3.49% of EGFR mutant LUDA patients. The 2 most common EGFR ex20ins subtypes were S768_D770dup and A767_V769dup, which together accounted for 55.84% of the EGFR ex20ins cases. About 61% (14/23) of the EGFR ex20ins subtypes occurred only once. Additionally, 8 of the EGFR ex20ins subtypes were not recorded in the COSMIC database. These results showed that the EGFR ex20ins mutations were highly heterogeneous. There was no significant difference in the frequency and distribution of EGFR ex20ins mutations between Chinese and Western LUAD patients, but the frequency of EGFR ex20ins mutations was significantly lower in EGFR-mutant Chinese LUAD patients than Western LUAD patients. The co-mutation analysis showed that EGFR ex20ins occurred significantly and exclusively with certain driver genes in LUAD, including ALK fusion (χ2=7.133, P=0.008), KRAS (χ2=8.468, P=0.004), and PIK3CA (χ2=5.792, P=0.016). No gene was observed to be significantly co-mutated with EGFR ex20ins. In general, patients with EGFR ex20ins shared a similar age and gender to patients with other EGFR mutations or without EGFR ex20ins.
Conclusions:
Overall, our results revealed the molecular and clinicopathologic features of EGFR ex20ins in Chinese LUAD patients, which will be helpful for drug development and in clinical trials targeting EGFR ex20ins.
Insights
Epidermal growth factor receptor exon 20 insertions (EGFR ex20ins) are diverse lung cancer mutations. This study details their features in Chinese patients, aiding targeted therapy development.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Epidermal growth factor receptor exon 20 insertions (EGFR ex20ins) represent a subset of EGFR mutations in lung adenocarcinoma (LUAD).
- Despite approved targeted therapies, the heterogeneity and underdetection of EGFR ex20ins limit their accurate frequency assessment.
- Understanding the molecular and clinicopathologic landscape of EGFR ex20ins is crucial for optimizing patient stratification and treatment strategies.
Purpose of the Study:
- To investigate the molecular and clinicopathologic characteristics of EGFR ex20ins in a large cohort of Chinese LUAD patients.
- To compare the frequency and distribution of EGFR ex20ins mutations between Chinese and Western LUAD populations.
- To identify potential co-occurring mutations associated with EGFR ex20ins to inform targeted therapy development.
Main Methods:
- Next-generation sequencing (NGS) was employed to analyze EGFR ex20ins in 3,892 Chinese LUAD patients.
- Data from this study were integrated with previous studies to compare mutation frequencies and distributions between Chinese and Western cohorts.
- Co-mutation analysis was performed to identify genes frequently co-occurring with EGFR ex20ins.
Main Results:
- 23 unique EGFR ex20ins were identified in 77 LUAD patients (1.98% of all LUAD; 3.49% of EGFR-mutant LUAD).
- High heterogeneity was observed, with 61% of subtypes occurring only once and 8 subtypes not found in the COSMIC database.
- EGFR ex20ins showed significant co-occurrence with ALK fusion, KRAS, and PIK3CA, but not exclusively with other specific driver genes.
Conclusions:
- The study elucidates the molecular and clinicopathologic features of EGFR ex20ins in Chinese LUAD patients, highlighting significant heterogeneity.
- Findings indicate no significant difference in EGFR ex20ins distribution between Chinese and Western populations, though frequency is lower in Chinese EGFR-mutant LUAD.
- The identified co-mutations provide valuable insights for future drug development and clinical trial designs targeting EGFR ex20ins.
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