Molecular Profile of Lung Adenocarcinoma in Brazilian Never-Smokers.

e20611 Background: Lung adenocarcinoma in never-smokers (LANS) is a disease largely defined by targetable oncogenic mutations. High frequency of actionable genomic alterations has been reported in cohorts from different regions worldwide. Particularly in Asian cohorts, rates of clinically relevant mutations reach almost 90% of LANS. However, great variance between different geographic regions was found. In Brazil, the molecular profile of LANS is unknown. Methods: Consecutive cases of never-smokers with lung adenocarcinoma treated at the Brazilian National Cancer Institute from 2011 to 2013 were selected. DNA was extracted from formalin-fixed paraffin-embedded tissue and genotyped for 409 cancer-related genes by Next Generation Sequencing (NGS). All patients had been previously tested for EGFRmutations in Exons 18-21 either by Sanger or RT-PCR in a clinical laboratory. In tumours without a targetable alteration, a gene fusion panel was performed. Results: Sixteen patients had tumour block available for genotyping. The 409 NGS gene-panel detected 53 individual actionable mutations (median 3 per sample; range 0-10) in 15 (out of 16) tumours. The most commonly mutated genes were EGFR (15%,n = 8 of 53), STED2 (9%,n = 5 of 53), TP53 (7%,n = 4 of 53) and ERBB3 (7%,n = 4 of 53). Six cases (37%) harboured EGFR sensitizing mutations (1 L858R; 5 exon 19 deletions), some of which had not been previously detected by other technologies. The fusion panel identified 2 additional EML4-ALK rearrangements. No overlap was found between classic driver alterations. Overall, twelve out of 16 patient samples tested (75%) harboured a genomic alteration with a target agent based on NCCN guidelines (2 EGFR L858R; 6 EGFR exon 19 deletions; 2 ERBB2 mutations, 2 EML4-ALK). All four remaining patients without a oncogenic mutation considered targetable by NCCN, had at least one actionable genomic alteration identified. Conclusions: A broad genomic testing approach revealed a high prevalence of clinically relevant genetic alterations in Brazilian never-smoker with lung adenocarcinoma.