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• W2336809232 abstract "The detection of rare EGFR gene mutations creates many problems in qualifying NSCLC patients for TKI EGFR treatment. Indeed, it does not determine the efficacy of TKI EGFR in patients with these mutations, especially in carriers of exon 18 or 20 mutations. Moreover, the frequency of rare EGFR gene mutations in NSCLC patients is not precisely estimated. The European largest study of Beau-Faller et al. had examined exon 18 and 20 mutations in EGFR gene in 10 117 NSCLC Caucasian patients at 15 French National Cancer Institute platforms of the ERMETIC-IFCT network [1.Faller-Beau M. Prim N. Ruppert A.M. et al.Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10117 patients: a French ERMETIC-IFCT network.Ann Oncol. 2014; 25: 126-131Abstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar]. Lu et al. had collected EGFR mutation status and demographic data from 9926 questionnaire of NSCLC Asian patients (48 China hospitals) [2.Lu S. Li Z. Niu X. et al.Molecular epidemiology of EGFR mutations in 7953 non-small cell lung cancer of Chinese ethnicity.J Clin Oncol. 2014; 32 (suppl abstr e19009)Crossref Google Scholar]. IGNITE study enrolled 2291 Asian and 924 Russia patients to EGFR mutation testing [3.Han B. Tjulandin S. Hagiwara K. et al.Determining the prevalence of EGFR mutations in Asian and Russian patients (pts) with advanced non-small-cell lung cancer (aNSCLC) of adenocarcinoma (ADC) and non-ADC histology: IGNITE study.Ann Oncol. 2015; 26: i29-i44Google Scholar]. Our study is the third largest in the world and the second on Caucasians, just before the group of Skov et al. involving 1256 Danish patients [4.Skov B.G. Hogdall E. Clementsen P. et al.The prevalence of EGFR mutations in non-small cell lung cancer in an unselected Caucasian population.APMIS. 2014; 123: 108-115Crossref PubMed Scopus (48) Google Scholar] and the group of Rosell et al. involving 2105 Spanish patients [5.Rosell R. Moran T. Quearalt C. et al.Screening for epidermal growth factor receptor mutations in lung cancer.N Engl J Med. 2009; 361: 958-967Crossref PubMed Scopus (2097) Google Scholar]. These studies had used a different methodology starting from sequencing technologies (including next generation sequencing) [1.Faller-Beau M. Prim N. Ruppert A.M. et al.Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10117 patients: a French ERMETIC-IFCT network.Ann Oncol. 2014; 25: 126-131Abstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar, 4.Skov B.G. Hogdall E. Clementsen P. et al.The prevalence of EGFR mutations in non-small cell lung cancer in an unselected Caucasian population.APMIS. 2014; 123: 108-115Crossref PubMed Scopus (48) Google Scholar] by real-time PCR tests routinely used in diagnostic [2.Lu S. Li Z. Niu X. et al.Molecular epidemiology of EGFR mutations in 7953 non-small cell lung cancer of Chinese ethnicity.J Clin Oncol. 2014; 32 (suppl abstr e19009)Crossref Google Scholar, 3.Han B. Tjulandin S. Hagiwara K. et al.Determining the prevalence of EGFR mutations in Asian and Russian patients (pts) with advanced non-small-cell lung cancer (aNSCLC) of adenocarcinoma (ADC) and non-ADC histology: IGNITE study.Ann Oncol. 2015; 26: i29-i44Google Scholar] and finally laboratory-defined methods dedicated only for common-mutation detection [5.Rosell R. Moran T. Quearalt C. et al.Screening for epidermal growth factor receptor mutations in lung cancer.N Engl J Med. 2009; 361: 958-967Crossref PubMed Scopus (2097) Google Scholar]. Moreover, the populations were heterogeneous in terms of pathologic diagnoses. We routinely diagnosed rare and common EGFR gene mutations in 3856 Polish NSCLC patients using EGFR Mutation Analysis Kit for Real-Time PCR (Entrogen). 63.7% of formalin-fixed paraffin-embedded tissue and 36.3% of cytology were tested. Women accounted for 39.4% and adenocarcinoma was diagnosed in 88.6% [no squamous cell carcinoma (SQC)]. EGFR mutations were diagnosed in 325 patients (8.43%) including 64 patients (1.66%) with rare EGFR mutations. Deletions in exon 19 consisted of 50.46% all tested mutations, substitution L858R in exon 21–29.85%, rare mutations 14.77% and complex mutations 4.92%. The most common rare mutations were insertions in exon 20, substitution L861Q, G719X and S768I wherein, the last two mutations often coexisted (Figure 1A). We have read with special great attention the recent manuscript by Beau-Faller et al. published in Annals of Oncology (French ERMETIC-IFCT network) [1.Faller-Beau M. Prim N. Ruppert A.M. et al.Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10117 patients: a French ERMETIC-IFCT network.Ann Oncol. 2014; 25: 126-131Abstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar]. We obtained partially different results through differences in methodology or heterogeneity of the study groups (no data on the percentage of SQC in French study). The prevalence of exon 18 and 20 mutations (after exclusion of E709X and other exon 18 substitution, deletion or insertion that are not diagnosed by our in vitro diagnostics test) were 0.89% in French ERMETIC-IFCT network and 1.4% in our study (P = 0.0075). The frequency of exon 20 insertions was similar in both studies. However, we observed significantly higher percentage of complex mutations (P = 0.0057) and lower percentage of G719X substitution (P = 0.029) in comparison to French study (Figure 1B). The prevalence of mutations in exons 18 and 20 in the Danish study was even lower at 0.63% (7 patients with insertions in exon 20, G719X and S768I substitutions; this study included patients with SQC) [4.Skov B.G. Hogdall E. Clementsen P. et al.The prevalence of EGFR mutations in non-small cell lung cancer in an unselected Caucasian population.APMIS. 2014; 123: 108-115Crossref PubMed Scopus (48) Google Scholar]. IGNITE study did not detect the insertion in exon 20 and only single G719X substitution in Russian patients. Rare EGFR mutations may not be as rare as previously thought, but a correct assessment of their frequency requires the analysis of very large patient populations. The authors have declared no conflicts of interest." @default.
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• W2336809232 title "Prevalence of rare EGFR gene mutations in nonsmall-cell lung cancer: a multicenter study on 3856 Polish Caucasian patients" @default.
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