p.Leu747Pro mutation leads to misdiagnosis in EGFR mutation assessment - first Caucasian NSCLC patients reported

Epidermal growth factor receptor (EGFR) mutation assessment is essential for targeted therapy of non-small cell lung cancer (NSCLC) as predictive biomarker of the response to EGFR tyrosine kinase inhibitors (TKI).There is a number of well-known mutations in EGFR gene. Still infrequent or complex aberrations are also observed. p.Leu747Pro is one of rare mutations which might be misdiagnosed by commercial real-time PCR kits for EGFR mutation analysis. It is an inhibiting mutation. Importantly, it might be confused with an activating deletion in exon 19 of EGFR gene.The aim of the study was to assess the occurrence of p.Leu747Pro in a group of 1841 NSCLC patients referred for EGFR mutation analysis between 2015 and 2017.EGFR mutation analysis was performed with CE-IVD real-time PCR kit.The frequency of EGFR gene mutations was 8,4% (n=155), including deletions in exon 19 (n=84; 4,6%), p.Leu858Arg (n=56; 3%), insertions in exon 20 (n=9), p.Glu719X (n=1), p.Glu719X and p.Ser768Ile (n=5).All samples with a deletion in exon 19 were reanalysed by validated PNA-LNA PCR clamp to confirm the test result. In case of a discrepancy, Sanger sequencing was performed.Upon reanalysis, in 4 (4,8%) cases initially diagnosed as a deletion in exon 19, p.Leu747Pro substitution was decisively detected instead and confirmed with direct sequencing. All four NSCLC subjects (3 female, 1 male, average age 61) were diagnosed with adenocarcinoma. Clinical follow-up of patients harbouring c.Leu747Pro mutatio...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Molecular Pathology and Functional Genomics Source Type: research