Sujin Park1, Soomin Ahn2, Deok Geun Kim3,4, Hyunjin Kim1,5, So Young Kang1, Kyoung-Mee Kim1,3,5. 1. Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 2. Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; suminy317@gmail.com. 3. Department of Clinical Genomic Center, Samsung Medical Center, Seoul, Republic of Korea. 4. Department of Digital Health, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea. 5. Center of Companion Diagnostics, Samsung Medical Center, Seoul, Republic of Korea.
Abstract
BACKGROUND/AIM: ERBB2 mutation is an emerging therapeutic target in solid tumors; its therapeutic responses depend on the location of mutation. In gastric cancer, the profiles of ERBB2 mutations and their relationship with human epidermal growth factor receptor 2 (HER2) overexpression remain unknown. We aimed to describe the details of ERBB2 mutations in gastric cancer. PATIENTS AND METHODS: Comprehensive panel sequencing was performed in 234 advanced gastric cancer patients. We investigated hotspots and clinicopathologic features of ERBB2 mutant gastric cancer in a single institute and evaluated the hotspots of ERBB2 mutation in a public database. RESULTS: Eighteen patients (7.7%) had ERBB2 mutations. The most frequent mutation was p.Arg678Gln (42.1%), which was located in the juxtamembrane domain and was the most common mutation in public databases (20.5%). All 18 ERBB2-mutant patients were negative for HER2 expression. Co-occurring genetic alterations included KRAS, PIK3CA, and ATM mutations. CONCLUSION: ERBB2 mutations were not associated with HER2 overexpression in gastric cancer patients. The most common mutation was located in the juxtamembrane domain of ERBB2.
BACKGROUND/AIM: ERBB2 mutation is an emerging therapeutic target in solid tumors; its therapeutic responses depend on the location of mutation. In gastric cancer, the profiles of ERBB2 mutations and their relationship with human epidermal growth factor receptor 2 (HER2) overexpression remain unknown. We aimed to describe the details of ERBB2 mutations in gastric cancer. PATIENTS AND METHODS: Comprehensive panel sequencing was performed in 234 advanced gastric cancer patients. We investigated hotspots and clinicopathologic features of ERBB2 mutant gastric cancer in a single institute and evaluated the hotspots of ERBB2 mutation in a public database. RESULTS: Eighteen patients (7.7%) had ERBB2 mutations. The most frequent mutation was p.Arg678Gln (42.1%), which was located in the juxtamembrane domain and was the most common mutation in public databases (20.5%). All 18 ERBB2-mutant patients were negative for HER2 expression. Co-occurring genetic alterations included KRAS, PIK3CA, and ATM mutations. CONCLUSION: ERBB2 mutations were not associated with HER2 overexpression in gastric cancer patients. The most common mutation was located in the juxtamembrane domain of ERBB2.
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