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Twenty‐One Novel EGFR Kinase Domain variants in Patients with Nonsmall Cell Lung Cancer

Twenty‐One Novel EGFR Kinase Domain variants in Patients with Nonsmall Cell Lung Cancer Summary Somatic sequence variants in the epidermal growth factor receptor (EGFR) kinase domain are associated with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with nonsmall cell lung cancer (NSCLC). Patients exhibiting sequence variants in this domain that produce kinase activity enhancement, are more likely to benefit from TKIs than patients with EGFR wild‐type disease. Although most NSCLC EGFR‐related alleles are concentrated in a few positions, established protocols recommend sequencing EGFR exons 18–21. In this study, 21 novel somatic variants belonging to such exons in adult Argentinean patients affected with NSCLC are reported. Of these, 18 were single amino acid substitutions (SASs), occurring alone or in combination with another genetic alteration (complex cases), one was a short deletion, one was a short deletion‐short insertion combination, and one was a duplication. New variants and different combinations of previously reported variants were also found. Moreover, two of the reported SASs occurred in previously unreported positions of the EGFR kinase domain. In order to characterize the new sequence variants, physicochemical, sequence and conformational analyses were also performed. A better understanding of sequence variants in NSCLC may facilitate the most appropriate treatment choice for this complex disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Human Genetics Wiley

Twenty‐One Novel EGFR Kinase Domain variants in Patients with Nonsmall Cell Lung Cancer

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References (24)

Publisher
Wiley
Copyright
Copyright © 2015 John Wiley & Sons Ltd/University College London
ISSN
0003-4800
eISSN
1469-1809
DOI
10.1111/ahg.12127
pmid
26420346
Publisher site
See Article on Publisher Site

Abstract

Summary Somatic sequence variants in the epidermal growth factor receptor (EGFR) kinase domain are associated with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with nonsmall cell lung cancer (NSCLC). Patients exhibiting sequence variants in this domain that produce kinase activity enhancement, are more likely to benefit from TKIs than patients with EGFR wild‐type disease. Although most NSCLC EGFR‐related alleles are concentrated in a few positions, established protocols recommend sequencing EGFR exons 18–21. In this study, 21 novel somatic variants belonging to such exons in adult Argentinean patients affected with NSCLC are reported. Of these, 18 were single amino acid substitutions (SASs), occurring alone or in combination with another genetic alteration (complex cases), one was a short deletion, one was a short deletion‐short insertion combination, and one was a duplication. New variants and different combinations of previously reported variants were also found. Moreover, two of the reported SASs occurred in previously unreported positions of the EGFR kinase domain. In order to characterize the new sequence variants, physicochemical, sequence and conformational analyses were also performed. A better understanding of sequence variants in NSCLC may facilitate the most appropriate treatment choice for this complex disease.

Journal

Annals of Human Genetics – Wiley

Published: Nov 1, 2015

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