Related Experiment Video
Updated: May 29, 2026
Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
Functional mutation analysis of EGFR family genes and corresponding lymph node metastases in head and neck squamous
Takanori Hama1, Yuki Yuza, Toshihito Suda
1Division of Molecular Epidemiology, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.
Abstract:
Tumors with certain mutations in the epidermal growth factor receptor (EGFR) family genes dramatically respond to EGFR inhibitors. Therefore, these mutations are important factors that influence disease progression and patient survival. We previously studied the mutation status of EGFR in patients with head and neck squamous cell carcinoma (HNSCC). However, the mutation status of lymph node metastases and the frequency of mutations in EGFR family genes have not been extensively studied. In this study, we sequenced the catalytic domains of the three other members of the EGFR family, HER2, HER3, and HER4 in 92 clinical samples of HNSCC. We identified a HER2 mutation (K716E) in one sample but no mutations were found in HER3 or HER4. Next to investigate the relationship between EGFR mutations and tumor metastasis, we compared the DNA sequences of the EGFR gene between the primary tumor and the lymph node metastasis in 31 clinical samples. Only one of the patients with an EGFR mutation in the primary HNSCC carried the same mutation (L858R) in the lymph node metastasis. Finally, we explored the tumorigenic potential of the EGFR mutations that we had previously identified and their sensitivity to two different EGFR tyrosine kinase inhibitors (CL-387785, OSI-420). Ba/F3 cells transformed with mutant EGFR genes were sensitive to treatment with lower concentrations of CL-387785 than of OSI-420. These results contribute to our understanding of the genetic basis of drug sensitivity and will help design drugs that specifically target different subtypes of HNSCC.
Insights
Mutations in epidermal growth factor receptor (EGFR) family genes impact head and neck squamous cell carcinoma (HNSCC) progression. This study found limited HER2 mutations and investigated EGFR mutations in HNSCC metastasis and drug sensitivity.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) family gene mutations are crucial for targeted therapy in head and neck squamous cell carcinoma (HNSCC).
- Previous research focused on EGFR mutations, but the status of other EGFR family members (HER2, HER3, HER4) and mutations in lymph node metastases remains less understood.
Purpose of the Study:
- To investigate the mutation status of HER2, HER3, and HER4 in HNSCC.
- To analyze the presence and correlation of EGFR mutations between primary HNSCC tumors and lymph node metastases.
- To evaluate the tumorigenic potential and drug sensitivity of identified EGFR mutations.
Main Methods:
- Sequencing of catalytic domains of HER2, HER3, and HER4 in 92 HNSCC samples.
- Comparison of EGFR gene sequences between primary tumors and lymph node metastases in 31 HNSCC samples.
- Assessment of EGFR mutation sensitivity to tyrosine kinase inhibitors (CL-387785, OSI-420) using Ba/F3 cell models.
Main Results:
- A single HER2 mutation (K716E) was identified; no mutations were found in HER3 or HER4.
- One patient with primary HNSCC and an EGFR mutation also had the same mutation (L858R) in lymph node metastasis.
- Mutant EGFR-transformed Ba/F3 cells showed higher sensitivity to CL-387785 than OSI-420.
Conclusions:
- EGFR family gene mutations are infrequent in HNSCC, with limited evidence of HER2, HER3, or HER4 involvement.
- EGFR mutations in primary HNSCC may not consistently transfer to lymph node metastases.
- Differential sensitivity of mutant EGFR to tyrosine kinase inhibitors suggests potential for subtype-specific HNSCC drug design.
