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

Authors
Hasenahuer, Marcia Anahí; Parisi, Gustavo Daniel; Gautier, Marien; Lazarowski, Alberto Jorge; Bramuglia, Guillermo Federico; Fornasari, Maria Silvina
Publication Year
2015
Language
English
Format
article
Status
Published version
Description
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.
Fil: Hasenahuer, Marcia Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Gautier, Marien. Fundación Investigar; Argentina
Fil: Lazarowski, Alberto Jorge. Fundación Investigar; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Bramuglia, Guillermo Federico. Fundación Investigar; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Fornasari, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Subject
PROTEIN
VARIATIONS
HUMAN
DISEASE
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Ciencias de la Computación
Ciencias de la Computación e Información
CIENCIAS NATURALES Y EXACTAS
Salud Ocupacional
Ciencias de la Salud
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/42837