Prospective Comprehensive Genomic Profiling of Advanced Gastric Carcinoma Cases Reveals Frequent Clinically Relevant Genomic Alterations and New Routes for Targeted Therapies. (16th April 2015)

• Record Type: Journal Article
• Authors: Ali, Siraj M.; Sanford, Eric M.; Klempner, Samuel J.; Rubinson, Douglas A.; Wang, Kai; Palma, Norma A.; Chmielecki, Juliann; Yelensky, Roman; Palmer, Gary A.; Morosini, Deborah; Lipson, Doron; Catenacci, Daniel V.; Braiteh, Fadi; Erlich, Rachel; Stephens, Philip J.; Ross, Jeffrey S.; Ou, Sai-Hong Ignatius; Miller, Vincent A.
• Is Part Of: Oncologist. Volume 20:Number 5(2015)
• Page Start: 499
• Page End: 507
• Publication Date: 2015-04-16
• Subjects: Gastric cancer -- Sequencing -- Targeted therapy -- Mutation -- Profiling -- MET; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2014-0378
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: Background: Gastric cancer (GC) is a major global cancer burden and the second most common cause of global cancer-related deaths. The addition of anti-ERBB2 (HER2) targeted therapy to chemotherapy improves survival for ERBB2 -amplified advanced GC patients; however, the majority of GC patients do not harbor this alteration and thus cannot benefit from targeted therapy under current practice paradigms. Materials and Methods: Prospective comprehensive genomic profiling of 116 predominantly locally advanced or metastatic (90.0%) gastric cancer cases was performed to identify genomic alterations (GAs) associated with a potential response to targeted therapies approved by the U.S. Food and Drug Administration or targeted therapy-based clinical trials. Results: Overall, 78% of GC cases harbored one clinically relevant GA or more, with the most frequent alterations being found in TP53 (50%), ARID1A (24%), KRAS (16%), CDH1 (15%), CDKN2A (14%), CCND1 (9.5%), ERBB2 (8.5%), PIK3CA (8.6%), MLL2 (6.9%), FGFR2 (6.0%), and MET (6.0%). Receptor tyrosine kinase genomic alterations were detected in 20.6% of cases, primarily ERBB2, FGFR2, and MET amplification, with ERBB2 alterations evenly split between amplifications and base substitutions. Rare BRAF mutations (2.6%) were also observed. One MET -amplified GC patient responded for 5 months to crizotinib, a multitargeted ALK/ROS1/MET inhibitor. Conclusion: Comprehensive genomic profiling of GC identifies clinically relevant GAs that suggest benefit from targeted therapy including MET -amplified GC and ERBB2 base substitutions. Abstract : Prospective comprehensive genomic profiling of 116 predominantly locally advanced or metastatic gastric cancer (GC) cases was performed to identify genomic alterations (GAs) associated with a potential response to targeted therapies or targeted therapy-based clinical trials. Comprehensive genomic profiling of GC identified clinically relevant GAs that suggest benefit from targeted therapy including MET -amplified GC and ERBB2 base substitutions.