title: A cautionary lesson on the use of targeted methods for EGFR mutation analysis: a case report.
abstract: Epidermal growth factor receptor (EGFR) mutation analysis is recommended for lung cancer patients prior to the prescription of first-line EGFR tyrosine kinase inhibitors in order to predict response to treatment. There are many methods available to identify mutations in the EGFR gene; a large number of clinical laboratories use the therascreen EGFR RGQ PCR kit (Qiagen). We report a case where this kit detected an exon 19 deletion, predicting sensitivity to tyrosine kinase inhibitors (TKIs), which on further analysis was found to be a 2 bp indel (c.2239_2240delinsCC, p.(Leu747Pro)). Two of four published cases with this mutation were found to be associated with resistance to EGFR TKI. The sample was also tested using two other commercial kits, one of which indicated a deletion. This is a rare mutation making the erroneous detection of a deletion unlikely; however, it is important that clinical laboratories are aware of the potential failings of two commercial kits for EGFR mutation analysis.
authors.affiliation: Department of Molecular Pathology, NHS Lothian, Edinburgh, UK.
authors.forename: K
authors.initials: K
authors.lastname: Walsh
authors.affiliation: Department of Pathology, NHS Lothian, Edinburgh, UK.
authors.forename: W A
authors.initials: WA
authors.lastname: Wallace
authors.affiliation: Department of Molecular Genetics, Institute of Medical Genetics, Cardiff, UK.
authors.forename: R
authors.initials: R
authors.lastname: Butler
authors.affiliation: Department of Clinical Oncology, NHS Lothian, Edinburgh, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Mackean
authors.affiliation: Department of Pathology, NHS Lothian, Edinburgh, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Harrison
authors.affiliation: Department of Haematology, NHS Lothan, Edinburgh, UK.
authors.forename: D
authors.initials: D
authors.lastname: Stirling
authors.affiliation: Department of Molecular Pathology, NHS Lothian, Edinburgh, UK.
authors.forename: A
authors.initials: A
authors.lastname: Oniscu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Egfr; Lung Cancer; Molecular Pathology