Abstract

EGFR-TKIs have been the standard first-line treatment for metastatic NSCLC patients with sensitive EGFR-mutants, meanwhile, other drugs target different driver mutants like BRAF-inhibitor dabrafenib has shown promising efficacy for metastatic BRAF-mutated NSCLC patients. Therefore, spotting patients carrying the targeted mutations is of great significance. However, molecular detection methods applied in clinical practice, especially detection of BRAF in NSCLC patients needs further exploration. Therefore, more sensitive and economic methods are required. We applied the CastPCR technology to the molecular detection of EGFR (del2235-2249, del2236-2250, T790M, L858R) and BRAF (V600E, G469A, D594G) mutations in 144 treatment-naive adenocarcinomas of the lung, and analyzed the association between the mutation rates and patients' clinicopathological features. EGFR mutation: 74 (51.4%, 74/144) cases were identified harboring EGFR mutations. 58 (40.3%, 58/144) carried sensitizing mutations (19Del or L858R) and 21 (14.6%, 21/144) carried resistant mutations (T790M). 10 (6.9%, 10/144) mutation-positive patients were double-mutated. EGFR mutation rate was significantly higher in female compared with that of males (60.9% v.s. 43.8%, P<0.05), in non-smokers compared with that of smokers (62.8% v.s. 34.5%, P<0.05). BRAF mutation:12 (8.3%, 12/144) patients were identified with BRAF mutations. 2 were V600E (16.7%, 2/12) and 10 (83.3%, 10/12) were non-V600E. Among the 10 non-V600E mutations, D594G accounted for 9 (90.0%,9/10) and G469A accounted for only 1 (10.0%, 1/10). Statistical analysis demonstrated that BRAF mutation rate was not associated with any of the clinicopathological features: age, gender, smoking status, differentiation degree, tumor size, regional lymph nodes metastasis and distant metastasis of (P≥0.05). The CastPCR technology is a robust method with high sensitivity for molecular detecting of EGFR and BRAF mutations in clinical FFPE samples.

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