Reference Detail

Ref Type

Journal Article

PMID

(22190593)

Authors

He M, Capelletti M, Nafa K, Yun CH, Arcila ME, Miller VA, Ginsberg MS, Zhao B, Kris MG, Eck MJ, Jänne PA, Ladanyi M, Oxnard GR

Title

EGFR exon 19 insertions: a new family of sensitizing EGFR mutations in lung adenocarcinoma.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	18	6	2012 Mar 15	1790-7	Clin Cancer Res

URL

Abstract Text

Epidermal growth factor receptor (EGFR) genotyping is now standard in the management of advanced lung adenocarcinoma, as this biomarker predicts marked benefit from treatment with EGFR tyrosine kinase inhibitors (TKI). EGFR exon 19 insertions are a poorly described family of EGFR mutations, and their association with EGFR-TKI sensitivity in lung adenocarcinoma is uncertain.Patients with lung cancers harboring EGFR exon 19 insertions were studied. The predicted effects of the insertions on the structure of the EGFR protein were examined, and EGFR exon 19 insertions were introduced into Ba/F3 cells to assess oncogenicity and in vitro sensitivity to EGFR-TKIs. In patients receiving TKI, response magnitude was assessed with serial computed tomographic (CT) measurement.Twelve tumors harboring EGFR exon 19 insertions were identified; patients were predominately female (92%) and never-smokers (75%). The 11 specimens available for full sequencing all showed an 18-bp insertion that resulted in the substitution of a Pro for Leu at residue 747. The mutant EGFR transformed the Ba/F3 cells, which were then sensitive to EGFR-TKI. Six patients with measurable disease received TKI and five had a response on serial CT.EGFR exon 19 insertions are a newly appreciated family of EGFR-TKI-sensitizing mutations, and patients with tumors harboring these mutations should be treated with EGFR-TKI. While these mutations may be missed through the use of some mutation-specific assays, the addition of PCR product size analysis to multigene assays allows sensitive detection of both exon 19 insertion and deletion mutations.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References