Prospective Comprehensive Genomic Profiling of Advanced Gastric Carcinoma Cases Reveals Frequent Clinically Relevant Genomic Alterations and New Routes for Targeted Therapies

摘要: Background. Gastric cancer (GC) is a major global burden and the second most common cause of cancer-related deaths. The addition anti-ERBB2 (HER2) targeted therapy to chemotherapy improves survival for ERBB2-amplifiedadvancedGCpatients;however,themajority GC patients do not harbor this alteration thus cannot benefit from under current practice paradigms. Materials Methods. Prospective comprehensive genomic profiling 116 predominantly locally advanced or metastatic (90.0%) gastric cases was performed identify alterations(GAs)associatedwithapotentialresponsetotargeted therapiesapprovedbytheU.S.FoodandDrug Administrationor therapy-based clinical trials. Results. Overall, 78% harbored one clinically relevant GAormore,withthemostfrequentalterationsbeingfoundinTP53 (50%), ARID1A (24%), KRAS (16%), CDH1 (15%), CDKN2A (14%), CCND1 (9.5%), ERBB2 (8.5%), PIK3CA (8.6%), MLL2 (6.9%), FGFR2 (6.0%), MET (6.0%). Receptor tyrosine kinase alterations were detected in 20.6% cases, primarily ERBB2, FGFR2, andMETamplification,withERBB2alterationsevenlysplitbetween amplifications base substitutions. Rare BRAF mutations (2.6%) also observed. One MET-amplified patient responded 5 months crizotinib, multitargeted ALK/ROS1/MET inhibitor. Conclusion. ComprehensivegenomicprofilingofGCidentifies GAs that suggest including Oncologist 2015;20:1–9 ImplicationsforPractice:Despitedescriptionofmanypotentiallyclinicallyrelevantgenomicalterationsinretrospectiveresearch studies, these are regularly assessed manner practice.This study demonstratesthe feasibility prospective (CGP) carcinoma. We demonstrated high frequency associated with potential therapies. CGP setting may inform therapeutic options beyond standard care testing by identifying such as point domain amplification. Genotype-directed management highlighted response carcinoma crizotinib.