EGFR exon 19 insertions: A new family of sensitizing EGFR mutations in lung adenocarcinoma Journal Article

Authors: He, M.; Capelletti, M.; Nafa, K.; Yun, C. H.; Arcila, M. E.; Miller, V. A.; Ginsberg, M. S.; Zhao, B.; Kris, M. G.; Eck, M. J.; Jänne, P. A.; Ladanyi, M.; Oxnard, G. R.
Article Title: EGFR exon 19 insertions: A new family of sensitizing EGFR mutations in lung adenocarcinoma
Abstract: Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: 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 ofPCR product size analysis to multigene assays allows sensitive detection of both exon 19 insertion and deletion mutations. ©2011 AACR.
Journal Title: Clinical Cancer Research
Volume: 18
Issue: 6
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2012-03-15
Start Page: 1790
End Page: 1797
Language: English
DOI: 10.1158/1078-0432.ccr-11-2361
PROVIDER: scopus
PMCID: PMC3306520
PUBMED: 22190593
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 2 April 2012" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Khedoudja Nafa
    181 Nafa
  2. Michelle S Ginsberg
    158 Ginsberg
  3. Binsheng Zhao
    46 Zhao
  4. Vincent Miller
    261 Miller
  5. Marc Ladanyi
    863 Ladanyi
  6. Maria Eugenia Arcila
    336 Arcila
  7. Mark Kris
    597 Kris
  8. Mai He
    6 He