Assessment of a highly curated somatic oncology mutation database to facilitate identification of clinically important variants in NGS results.

• DOI: 10.1200/jco.2019.37.15_suppl.e18086
• Publication Date: 2019-05-27T16:11:37Z
• Authors: Xiaoju Max Ma; Stephanie J. Yaung; Liu Xi; Christine Ju; John F. Palma; Maximilian Schmid
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

e18086 Background: The increasing adoption of Next Generation Sequencing (NGS) in molecular profiling cancer presents a growing need for streamlined interpretation NGS results clinical labs. This can be achieved through bioinformatics tools equipped with highly-curated database on clinically important variants. Methods: We performed an initial assessment result tool called NAVIFY Mutation Profiler (NMP), which enabled us to process Variant Call Format (VCF) file and generate report consensus recommendations NCCN, ASCO, CAP ACMG. annotation identifies pathogenic variants unknown significance (VUS), groups by AMP Tiers. At the time this assessment, NMP contained curation ~4,000 In study, we used from 38 anonymized cases known treatment regimens retrospectively assess as variant tool. Our cohort lung subjects treated EGFR tyrosine kinase inhibitor (TKI) (5 cases), well relapsed against TKI (1 case) or ALK crizotinib (22 cases). also included 10 control where standard care chemo was because diagnostic methods did not reveal any actionable targets. Results: annotated VCF data generated within minutes per case although some > 100 correctly associated therapies options corresponding 5 cases. As expected, recommend targeted chemo-treated For subject TKI, interpreted complex mutation profile containing both activating (L858R) drug-resistance (T790M) addition, out 22 crizotinib, marked 14 resistance when conferring detected. There limited no published evidence interpret remaining 8 resistance. Conclusions: study. With knowledge base, simplifies reporting identifying mutations associating qualified supporting evidence.