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Updated: Jul 19, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Epidermal growth factor receptor mutation in lung cancer are linked to bronchioloalveolar differentiation
Hélène Blons1, Jean-François Côté, Delphine Le Corre
1Department of Biochemistry, Hôpital Européen Georges Pompidou, Université Paris V, 75015 Paris, France.
Abstract:
In lung cancer, an association was made between drastic clinical response to epidermal growth factor receptor (EGFR) inhibitors and the presence of somatic mutations within the tyrosine kinase domain of the EGFR. In some cases, patients with partial response or disease stabilization do not always have EGFR-mutated tumors. To go further in the characterization of the EGF pathway, we screened EGFR, ERBB2, ERBB3, KRAS, BRAF, and PIK3CA for mutations in 2 groups of White patients with nonsmall cell lung cancer (45 cancers from women and 46 cancers from men). Associations between TP53 mutations, clinicopathologic parameters, and EGF pathway molecular alterations were analyzed. All mutations were exclusive and essentially found in EGFR and KRAS. We demonstrated that EGFR mutations were linked to female sex, absence of smoking, late age at diagnosis, and adenocarcinoma (ADC) with bronchioloalveolar (BAC) features. Moreover, in invasive ADC with BAC component, microdissection assays showed that mutations were retrieved in both tumor subtypes suggesting that EGFR mutations appear early in lung carcinogenesis. On the contrary, KRAS mutations correlated with smoking, younger age at diagnosis, and ADC subtype regardless of BAC differentiation. These results suggest the existence of distinct carcinogenesis pathways both leading to disruption of EGF regulation and targeted either by tobacco carcinogens or by unidentified toxic. The identification of BAC features in ADC helps clustering patients that are more likely to fit the EGFR-mutated group.
Insights
Epidermal growth factor receptor (EGFR) mutations in lung cancer are linked to specific patient and tumor characteristics. Identifying these mutations aids in understanding distinct cancer development pathways.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) inhibitors show variable efficacy in lung cancer.
- Somatic mutations in EGFR's tyrosine kinase domain correlate with response to EGFR inhibitors.
- Tumor response is not always explained by EGFR mutations alone.
Purpose of the Study:
- To investigate mutations in key genes of the EGF pathway (EGFR, ERBB2, ERBB3, KRAS, BRAF, PIK3CA) in non-small cell lung cancer (NSCLC).
- To analyze associations between TP53 mutations, clinicopathologic features, and EGF pathway alterations.
- To elucidate distinct molecular pathways in lung carcinogenesis.
Main Methods:
- Screening of EGFR, ERBB2, ERBB3, KRAS, BRAF, and PIK3CA for mutations in 45 female and 46 male NSCLC patients.
- Analysis of TP53 mutations and their correlation with clinicopathologic parameters and EGF pathway alterations.
- Microdissection assays on invasive adenocarcinoma with bronchioloalveolar (BAC) features.
Main Results:
- Mutations were exclusive, primarily found in EGFR and KRAS.
- EGFR mutations associated with female sex, non-smoking status, older age, and adenocarcinoma (ADC) with BAC features.
- KRAS mutations correlated with smoking, younger age, and ADC subtype without BAC differentiation.
- EGFR mutations were detected early in lung carcinogenesis within invasive ADC with BAC components.
Conclusions:
- Distinct carcinogenesis pathways exist, leading to EGF pathway dysregulation.
- EGFR mutations are linked to specific demographic and histopathologic features in NSCLC.
- KRAS mutations are associated with different risk factors and tumor subtypes.
- Identifying BAC features in ADC can help select patients likely to benefit from EGFR-targeted therapies.
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