title: Twenty-One Novel EGFR Kinase Domain variants in Patients with Nonsmall Cell Lung Cancer.
abstract: 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.
authors.affiliation: Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 352, Bernal, (B1876BXD), Buenos Aires, Argentina.
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Hasenahuer
authors.affiliation: Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 352, Bernal, (B1876BXD), Buenos Aires, Argentina.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Parisi
authors.affiliation: Fundación Investigar. Riobamba 429 Piso 15, Ciudad Autónoma de Buenos Aires, (C1022AAT), Argentina.
authors.forename: Marien
authors.initials: M
authors.lastname: Gautier
authors.affiliation: Fundación Investigar. Riobamba 429 Piso 15, Ciudad Autónoma de Buenos Aires, (C1022AAT), Argentina.|Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, Ciudad Autónoma de Buenos Aires, (C1113AAD), Argentina.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lazarowski
authors.affiliation: Fundación Investigar. Riobamba 429 Piso 15, Ciudad Autónoma de Buenos Aires, (C1022AAT), Argentina.|Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, Ciudad Autónoma de Buenos Aires, (C1113AAD), Argentina.
authors.forename: Guillermo F
authors.initials: GF
authors.lastname: Bramuglia
authors.affiliation: Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 352, Bernal, (B1876BXD), Buenos Aires, Argentina.
authors.forename: Maria Silvina
authors.initials: MS
authors.lastname: Fornasari
mesh_terms: D019943:Amino Acid Substitution; D001118:Argentina; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; lung cancer; new sequence variations; tyrosine kinases