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Oncologist. 2015 May;20(5):499-507. doi: 10.1634/theoncologist.2014-0378. Epub 2015 Apr 16.

Prospective comprehensive genomic profiling of advanced gastric carcinoma cases reveals frequent clinically relevant genomic alterations and new routes for targeted therapies.

Author information

1
Foundation Medicine Inc., Cambridge, Massachusetts, USA; Chao Family Comprehensive Cancer Center, Division of Hematology-Oncology, Department of Medicine, University of California Irvine School of Medicine, Orange, California, USA; Dana-Farber Cancer Institute, Boston, Massachusetts, USA; University of Chicago, Chicago, Illinois, USA; Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada, USA; Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA Siraj@Foundationmedicine.com.
2
Foundation Medicine Inc., Cambridge, Massachusetts, USA; Chao Family Comprehensive Cancer Center, Division of Hematology-Oncology, Department of Medicine, University of California Irvine School of Medicine, Orange, California, USA; Dana-Farber Cancer Institute, Boston, Massachusetts, USA; University of Chicago, Chicago, Illinois, USA; Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada, USA; Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA.

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.

KEYWORDS:

Gastric cancer; MET; Mutation; Profiling; Sequencing; Targeted therapy

PMID:
25882375
PMCID:
PMC4425384
DOI:
10.1634/theoncologist.2014-0378
[Indexed for MEDLINE]
Free PMC Article

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