Database of somatic mutations in EGFR with analyses revealing indel hotspots but no smoking‐associated signature

摘要: We created an Epidermal Growth Factor Receptor (EGFR) Mutation Database (http://www.cityofhope.org/cmdl/egfr_db) that curates a convenient compilation of somatic EGFR mutations in non-small-cell lung cancer (NSCLC) and associated epidemiological methodological data, including response to the tyrosine kinase inhibitors Gefitinib Erlotinib. Herein, we analyze 809 collected from 26 publications. Four super hotspots account for 70% reported while two-thirds 131 unique have been only once 11% mutations. Consistent with strong biological selection gain function, are virtually all missense substitutions or in-frame microdeletions, microinsertions, microindels (colocalized insertion deletion net loss 1-50 nucleotides). Microdeletions common region exon 19. Microindels, which 8% mutations, smaller inserted sequences (95% 1 5 bp) elevated 16-fold relative mouse human germline microindels. Microdeletions/microindels significantly more frequent responders Erlotinib (P = 0.003). In addition, smokers do not carry signatures mutagens cigarette smoke. Otherwise, mutation pattern does differ respect gender, age, tumor histology. The is central resource sequence variant data clinicians, geneticists, other researchers. Authors encouraged submit new publications variants be included database provide direct submissions via WayStation submission publication process (http://www.centralmutations.org).