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EGFR
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Interpretation 298
Tier 1
EGFR
Variants
EGFR L747P
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 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 L747P (c.2239_2240 TT>CC) is a rare missense compound substitution mutation in the Exon 19 and has been reported to be resistant to some EGFR inhibitors.

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. van der Wekken AJ, et al. A novel EGFR mutation in exon 19 showed stable disease after TKI treatment. J Thorac Oncol 2012;7(8):e8
  4. Wu JY, et al. Effectiveness of tyrosine kinase inhibitors on "uncommon" epidermal growth factor receptor mutations of unknown clinical significance in non-small cell lung cancer. Clin Cancer Res 2011;17(11):3812-21
  5. Yu G, et al. EGFR mutation L747P led to gefitinib resistance and accelerated liver metastases in a Chinese patient with lung adenocarcinoma. Int J Clin Exp Pathol 2015;8(7):8603-6
  6. Wu SG, et al. Frequent epidermal growth factor receptor gene mutations in malignant pleural effusion of lung adenocarcinoma. Eur Respir J 2008;32(4):924-30
Last updated: 2016-08-01 20:01:33 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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