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Frequency of EGFR Mutations among Thai Non-Small Cell Lung Cancer [NSCLC] Patients

Kriangpol Wiriyaukaradecha MSc1, Chakrit Bunyoo MSc1, Wandee Udomchaiprasertkul MSc1, Thaniya Sricharunrat MD2, Supinda Petchjorm MD2, Wisut Lamlertthon MD, MHSc3, Narongrit Sritana MSc1

Affiliation : 1 Molecular Biology and Genomic Research Laboratory, Division of Research and International Relations, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand 2 Department of Pathology, Chulabhorn Hospital, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand 3 Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand

Background : Tyrosine kinase inhibitor is an important drug for lung adenocarcinoma patients with epidermal growth factor [EGFR] mutation. Asian patients with non-small cell lung cancer [NSCLC] have a high incidence of EGFR mutations.
Objective : To determine the frequency of EGFR mutations among Thai NSCLC patients using Sanger sequencing and a real- time polymerase chain reaction [PCR] assay. Materials and Methods: DNA samples were extracted from formalin-fixed paraffin embedded [FFPE] tissues. EGFR mutations were analyzed by direct sequencing in 318 NSCLC cases and by a real-time PCR-based assay (therascreen® RGQ EGFR mutation kit) in 112 cases.
Results : With direct sequencing, EGFR mutations were detected in 156 of 318 cases (49.06%), including 101 exon 19 mutations (31.76%) and 89 exon 21 mutations (27.99%). Mutations in exons 18 through 21 were detected in 51.79% of the cases analyzed with the therascreen assay. Exon 19 deletion and L858R mutations were detected in 25.16% and 16.35% of cases, respectively, by direct sequencing and in 26.78% and 13.39% of cases, respectively, by the therascreen assay. T790M mutation, found in 7.14% of the cases, always occurred along with exon 19 deletion or L858R mutation. Patients aged >75 years had a significantly higher frequency of EGFR mutations than younger patients (p<0.05). In addition, female patients had a significantly higher frequency of EGFR mutation than male patients (p<0.001). EGFR mutations were detected at the same rate by direct sequencing and a real-time PCR assay.
Conclusion : This study supports that EGFR mutation is more prevalent in women and older (age >75) Asian patients with NSCLC. The two most common mutations are exon 19 deletion and L858R substitutions.

Keywords : Lung cancer, NSCLC, EGFR, Mutation, Tyrosine kinase inhibitor


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