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Interpretation 2351
Tier 1
EGFR
Variants
EGFR G796S
Primary Sites
Lung
Tumor Types
Non-Small Cell Lung Carcinoma
Adenocarcinoma
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 tyrosine kinase inhibitors (TKIs, 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. Exon 20 mutations are more commonly associated with resistance to tyrosine kinase inhibitors (TKIs), but may respond to third generation TKI (eg, osimertinib). This EGFR variant (G796S) lies within the tyrosine kinase domain and has been reported in rare cases of lung adenocarcinomas, squamous cell carcinoma of head and neck and prostate adenocarcinoma. In silico studies suggest G796S mutation may confer resistance to TKIs. However, additional studies are needed to further elucidate the oncogenicity of the mutation and therapeutic implications of this rare variant.

Citations
  1. Sequist LV, et al. First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations. J Clin Oncol 2008;26(15):2442-9
  2. Pao W, et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004;101(36):13306-11
  3. Pirker R Third-generation epidermal growth factor receptor tyrosine kinase inhibitors in advanced nonsmall cell lung cancer. Curr Opin Oncol 2016;28(2):115-21
  4. Ma C, et al. T790M and acquired resistance of EGFR TKI: a literature review of clinical reports. J Thorac Dis 2011;3(1):10-8
  5. Schwentner I, et al. Identification of the rare EGFR mutation p.G796S as somatic and germline mutation in white patients with squamous cell carcinoma of the head and neck. Head & neck 2008;30(8):1040-4
  6. Ou SI, et al. Emergence of novel and dominant acquired EGFR solvent-front mutations at Gly796 (G796S/R) together with C797S/R and L792F/H mutations in one EGFR (L858R/T790M) NSCLC patient who progressed on osimertinib. Lung cancer (Amsterdam, Netherlands) 2017;108:228-231
  7. Douglas DA, et al. Novel mutations of epidermal growth factor receptor in localized prostate cancer. Frontiers in bioscience: a journal and virtual library 2006;11:2518-25
  8. Goldberg ME, et al. Multiple configurations of EGFR exon 20 resistance mutations after first- and third-generation EGFR TKI treatment affect treatment options in NSCLC. PLoS One. 2018 Nov 27;13(11):e0208097.
Last updated: 2019-07-15 15:39:26 UTC
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