WCMC logo
PMKB
  • WCMC logoPMKB
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity
  • Login
EGFR
  • Information
  • View History
  • Pending Review
Interpretation 271
Tier 1
EGFR
Variants
EGFR K745_E746insIPVAIK
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Pleomorphic Carcinoma
Interpretation

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are present in approximately 80% of the lung adenocarcinomas that respond to first and second generation EGFR inhibitors (eg, gefitinib, erlotinib and afatinib). Two types of mutations account for approximately 80-90% of all EGFR mutations: short in-frame deletions in Exon 19 and a point mutation in exon 21 at codon 858 (L858R). Other less common mutations in exons 18, 20, and 21 are found in 10-20% of EGFR-mutated cases. EGFR Exon 19 deletions, EGFR Exon 21 L858R and EGFR Exon 18 G719 mutations correlate strongly with sensitivity to specific EGFR inhibitors and the response rate to therapy with TKIs has been reported to be up to 80% in such cases. The T790M mutation in exon 20 is associated with resistance to some EGFR inhibitors. However, third generation TKI (eg, osimertinib) can specifically target T790M. EGFR exon 19 in-frame insertions have been described in about 1% of EGFR-mutant lung cancers. They appear to be more common in nonsmoking women. These exon 19 insertions appear to be sensitizing mutations and have been shown to respond to TKIs in some studies.

Citations
  1. He M, et al. EGFR exon 19 insertions: a new family of sensitizing EGFR mutations in lung adenocarcinoma. Clin Cancer Res 2012;18(6):1790-7
  2. Agbarya A, et al. Getting out of a wheelchair: an uncommon insertion mutation in exon 19 of EGFR responsive to erlotinib. Springerplus 2014;3():507
  3. Iyevleva AG, et al. Lung carcinomas with EGFR exon 19 insertions are sensitive to gefitinib treatment. J Thorac Oncol 2014;9(4):e31-3
  4. Park J, et al. EGFR exon 19 insertions show good response to gefitinib, but short time to progression in Japanese patients. J Thorac Oncol 2014;9(2):e10-1
Last updated: 2016-05-18 23:02:30 UTC
PMKB Bot
  • Genes
  • Variants
  • Interpretations
  • Tumor Types
  • Primary Sites
  • Activity

Disclaimer: You assume full responsibility for all risks associated with using this PMKB website. The Englander Institute for Precision Medicine at Weill Cornell Medicine makes no guarantee of the comprehensiveness, reliability or accuracy of the information on this website and assumes no responsibility for errors in the information associated with this web site. Healthcare providers and patients must integrate all clinical and laboratory findings as well as information from a variety of sources before deciding on appropriate clinical care options.


When using PMKB, please cite: Huang et al., JAMIA 2017


HELP
User Guide
Video Tutorial
INFO
About
Latest
API
Twitter
CONTACT US
Contact

Englander Institute for Precision Medicine
© Weill Cornell Medicine | Version 1.7.2Privacy PolicyTerms of use