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Updated: Feb 19, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Mutational Landscape of DDR2 Gene in Lung Squamous Cell Carcinoma Using Next-generation Sequencing
Charles Ricordel1, Alexandra Lespagnol2, Francisco Llamas-Gutierrez3
1Department of Respiratory Medicine, Pontchaillou Hospital, Rennes 1 University, Rennes, France; Chemistry, Oncogenesis, and Stress Signaling, INSERM U1242, Centre Eugène Marquis, Rennes, France.
Background:
Lung cancer represents the leading cause of cancer-related death worldwide. Despite great advances in lung cancer management with the recent emergence of molecular targeted therapies for non-squamous non-small-cell lung cancer, no dramatic improvements have been achieved in lung squamous cell carcinoma (SCC). Mutations in discoidin domain receptor 2 (DDR2) gene were recently identified as promising molecular targets in this histology. The aim of this study is to describe the DDR2 mutational landscape of lung SCC and investigate the associated clinical factors.
Methods:
Next-generation sequencing of the DDR2 gene was performed on 271 samples of lung SCC. Patients followed in our institution from January 2011 to August 2014 were retrospectively selected for data collection. Other driver gene alterations (EGFR, KRAS, BRAF, HER2, and PI3KCA) were analyzed using pyrosequencing.
Results:
A total of 11 patients harboring a DDR2 mutation was detected among the 271 sequenced lung SCC samples (4%). We describe 10 unreported mutations, comprising a novel DDR2 exon 7 splice mutant. DDR2 mutations were not mutually exclusive with other driver gene alterations. One hundred thirty-six patients were included for clinical comparison and logistic regression analysis. No difference was detected between DDR2-mutant and DDR2 wild-type lung SCC regarding clinical characteristics or survival.
Conclusion:
DDR2 mutations were observed in 4% of cases of lung SCC of European descent. DDR2-mutated tumors can exhibit other driver gene alterations. No clinical characteristics were significantly associated with DDR2 mutation.
Insights
Discoidin domain receptor 2 (DDR2) mutations occur in 4% of lung squamous cell carcinoma (SCC) cases. These mutations were not associated with distinct clinical features or survival outcomes in the studied population.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Lung cancer remains a leading cause of cancer mortality globally.
- Lung squamous cell carcinoma (SCC) has seen limited therapeutic advances compared to other lung cancer subtypes.
- Mutations in the discoidin domain receptor 2 (DDR2) gene are emerging as potential therapeutic targets in lung SCC.
Purpose of the Study:
- To characterize the spectrum of DDR2 gene mutations in lung SCC.
- To identify potential clinical factors associated with DDR2 mutations in lung SCC patients.
Main Methods:
- Next-generation sequencing was used to analyze the DDR2 gene in 271 lung SCC samples.
- Retrospective data collection from patients treated between January 2011 and August 2014.
- Pyrosequencing was employed to detect alterations in other driver genes (EGFR, KRAS, BRAF, HER2, PIK3CA).
Main Results:
- DDR2 mutations were identified in 4% (11 out of 271) of lung SCC samples.
- Ten novel DDR2 mutations were described, including a new splice site mutation in exon 7.
- No significant differences in clinical characteristics or survival were observed between DDR2-mutant and DDR2 wild-type lung SCC.
Conclusions:
- DDR2 mutations are present in a subset (4%) of lung SCC, particularly in European populations.
- DDR2-mutated lung SCC can co-occur with other driver gene alterations.
- Clinical factors and survival outcomes are not significantly associated with DDR2 mutation status in lung SCC.
