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EGFR
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Interpretation 400
Tier 1
EGFR
Variants
EGFR S768I
EGFR V769L
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Non-Small Cell Lung 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 tyrosine kinase 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. EGFR S768I (exon 20) occurs in 1–2% of EGFR mutant lung cancers and is often coincident with other EGFR mutations. S768I and V769L have previously been identified in the same NSCLC tumors. There are conflicting data regarding the sensitivity to EGFR-TKIs of tumors harboring S768I and V769L mutations. Correlation with other clinical and laboratory findings is necessary.

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. Arcila ME, et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther 2013;12(2):220-9
  5. Hellmann MD, et al. Clinical and in vivo evidence that EGFR S768I mutant lung adenocarcinomas are sensitive to erlotinib. J Thorac Oncol 2014;9(10):e73-4
  6. Heigener DF, et al. Afatinib in Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations Pretreated With Reversible EGFR Inhibitors. Oncologist 2015;20(10):1167-74
  7. Improta G, et al. Epidermal growth factor receptor exon 20 p.S768I mutation in non-small cell lung carcinoma: A case report combined with a review of the literature and investigation of clinical significance. Oncol Lett 2016;11(1):393-398
Last updated: 2017-04-10 18:14:01 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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