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Updated: Aug 14, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
The epidermal growth factor receptor gene sequence is highly conserved in primary gastric cancers
Koshi Mimori1, Hisashi Nagahara, Tomoya Sudo
1Department of Surgery, Medical Institute of Bioregulation Kyushu University, Beppu, Japan.
Background And Objectives:
Recent studies have disclosed the presence of somatic mutations in the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancers (NSCLC), and susceptibility to the EGFR tyrosine kinase inhibitor (gefitinib) was determined by the presence of mutations in the kinase domain of this gene. We thus predicted a clinical benefit of gefitinib against the 12% of primary colorectal cancers exhibiting a mutation reflective of this potential distinctive susceptibility.
Patients And Methods:
The mutation status of the kinase domain in EGFR in different primary cancers has important clinical consequences, because the presence of a mutation is recognized as a reliable indicator for the effectiveness of gefitinib administration. In the current study, we investigated the presence of somatic mutations in exons 18-21 coding the ATP-binding domain in five gastric cancer cell lines and 39 primary gastric cancers and their corresponding normal tissues.
Results And Conclusions:
The kinase domain of EGFR is highly conserved in whole gastric cancer cell lines and cases, therefore treatment with gefitinib is unfortunately not recommended for such malignancy.
Insights
EGFR mutations predict gefitinib response in cancers. However, this study found EGFR kinase domain mutations are rare in gastric cancers, making gefitinib an unsuitable treatment for this malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Somatic mutations in the epidermal growth factor receptor (EGFR) gene are found in non-small cell lung cancers (NSCLC).
- Susceptibility to EGFR tyrosine kinase inhibitors like gefitinib is linked to specific mutations in the EGFR kinase domain.
Purpose of the Study:
- To investigate the presence of somatic mutations in the EGFR kinase domain (exons 18-21) in gastric cancer.
- To determine the potential clinical benefit of gefitinib in gastric cancer based on EGFR mutation status.
Main Methods:
- Analysis of EGFR mutation status in the kinase domain (exons 18-21) of five gastric cancer cell lines.
- Examination of EGFR mutation status in 39 primary gastric cancers and their corresponding normal tissues.
Main Results:
- The EGFR kinase domain was found to be highly conserved across all investigated gastric cancer cell lines and primary cases.
- No significant somatic mutations indicative of gefitinib susceptibility were identified in the studied gastric cancer samples.
Conclusions:
- The high conservation of the EGFR kinase domain in gastric cancer suggests a lack of the specific mutations targeted by gefitinib.
- Gefitinib treatment is not recommended for gastric cancer due to the absence of predictive EGFR mutations.
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