학술논문
Predominance of the Rare EGFR Mutation p.L861Q in Tunisian Patients with Non-Small Cell Lung Carcinoma
Document Type
Academic Journal
Author
Source
Genes. August 2022, Vol. 13 Issue 8
Subject
Language
English
ISSN
2073-4425
Abstract
Author(s): Rania Abdelmaksoud-Dammak [1]; Nihel Ammous-Boukhris [1]; Amèna Saadallah-Kallel [1]; Slim Charfi [2]; Souhir Khemiri [3]; Rim Khemakhem [4]; Nesrin Kallel [4]; Wala Ben Kridis-Rejeb [3]; Tahya Sallemi-Boudawara [2]; Afef [...]
Objectives: Several new cancer therapies targeting signaling pathways involved in the growth and progression of cancer cells were developed as personalized medicine. Our study aimed to identify epidermal growth factor receptor (EGFR) mutations for TKI treatment in non-small-cell lung cancer (NSCLC) Tunisian patients. Methods: Analysis of the TKI sensitivity mutations in exons 18 to 21 of the EGFR gene and exon 15 of the B-raf gene was performed in 79 formalin fixed-paraffin embedded (FFPE) NSCLC samples using pyrosequencing. Results: EGFR mutations were detected in 34 cases among 79 (43%), with the predominance of the L861Q in exon 21 found in 35.3% of the cases (12 out of 34). Deletions in exon 19 were found in 8 cases (23.5%), and only one young male patient had the T790M mutation. Three patients harbored composite EGFR mutations (p.E746_A750del/p.L861R, p.E746_S752>V/p.S768I, and p.G719A/p.L861Q). Furthermore, the EGFR mutated status was significantly more frequent in female patients (p = 0.019), in non-smoker patients (p = 0.008), and in patients with metastasis (p = 0.044). Moreover, the B-raf V600E was identified in 5 EGFR negative patients among 39 analyzed samples (13.15%). Conclusion: The p.L861Q localized in exon 21 of the EGFR gene was the most common mutation identified in our patients (35.3%), whereas the “classic” EGFR mutations such as Del19 and p.L858R were found in 23.5% and 11.7% of the cases, respectively. Interestingly, most of p.L861X mutation-carrying patients showed good response to TKI treatment. Altogether, our findings suggest a particular distribution of the EGFR-TKIs sensitivity mutations in Tunisian NSCLC patients.
Objectives: Several new cancer therapies targeting signaling pathways involved in the growth and progression of cancer cells were developed as personalized medicine. Our study aimed to identify epidermal growth factor receptor (EGFR) mutations for TKI treatment in non-small-cell lung cancer (NSCLC) Tunisian patients. Methods: Analysis of the TKI sensitivity mutations in exons 18 to 21 of the EGFR gene and exon 15 of the B-raf gene was performed in 79 formalin fixed-paraffin embedded (FFPE) NSCLC samples using pyrosequencing. Results: EGFR mutations were detected in 34 cases among 79 (43%), with the predominance of the L861Q in exon 21 found in 35.3% of the cases (12 out of 34). Deletions in exon 19 were found in 8 cases (23.5%), and only one young male patient had the T790M mutation. Three patients harbored composite EGFR mutations (p.E746_A750del/p.L861R, p.E746_S752>V/p.S768I, and p.G719A/p.L861Q). Furthermore, the EGFR mutated status was significantly more frequent in female patients (p = 0.019), in non-smoker patients (p = 0.008), and in patients with metastasis (p = 0.044). Moreover, the B-raf V600E was identified in 5 EGFR negative patients among 39 analyzed samples (13.15%). Conclusion: The p.L861Q localized in exon 21 of the EGFR gene was the most common mutation identified in our patients (35.3%), whereas the “classic” EGFR mutations such as Del19 and p.L858R were found in 23.5% and 11.7% of the cases, respectively. Interestingly, most of p.L861X mutation-carrying patients showed good response to TKI treatment. Altogether, our findings suggest a particular distribution of the EGFR-TKIs sensitivity mutations in Tunisian NSCLC patients.