Twenty novel EGFR kinase domain mutations in Argentinian patients with NSCLC

MARCIA HASENAUER; GUSTAVO PARISI; MARIEN GAUTIER; ALBERTO LAZAROWSKI; GUILLERMO BRAMUGLIA; MARIA SILVINA FORNASARI

ANNALS OF HUMAN GENETICS

WILEY-BLACKWELL PUBLISHING, INC

Año: 2015 p. 1 - 10

0003-4800

Somatic sequence variants in the epidermal growth factor receptor (EGFR) kinase domain are associated with sensitivityto tyrosine kinase inhibitors (TKIs) in patients with nonsmall cell lung cancer (NSCLC). Patients exhibiting sequencevariants in this domain that produce kinase activity enhancement, are more likely to benefit from TKIs than patients withEGFR wild-type disease. Although most NSCLC EGFR-related alleles are concentrated in a few positions, establishedprotocols recommend sequencing EGFR exons 18?21. In this study, 21 novel somatic variants belonging to such exons inadult 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 wasa short deletion-short insertion combination, and one was a duplication. New variants and different combinations ofpreviously reported variants were also found. Moreover, two of the reported SASs occurred in previously unreportedpositions of the EGFR kinase domain. In order to characterize the new sequence variants, physicochemical, sequenceand conformational analyses were also performed. A better understanding of sequence variants in NSCLC may facilitatethe most appropriate treatment choice for this complex disease.