Elke J A H van Beek1, Jonathan M Hernandez1,2, Debra A Goldman3, Jeremy L Davis1,2, Kaitlin McLaughlin2, R Taylor Ripley2, Teresa S Kim1, Laura H Tang4, Jaclyn F Hechtman4, Jian Zheng1, Marinela Capanu3, Nikolaus Schultz3,5,6, David M Hyman7, Marc Ladanyi4,5, Michael F Berger4,5,6, David B Solit5,6,7, Yelena Y Janjigian7, Vivian E Strong8. 1. Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 2. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. 3. Department of Epidemiology & Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 4. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 5. Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 6. Marie-Josée & Henry R. Kravis Center for Molecular Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 7. Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA. 8. Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. strongv@mskcc.org.
Abstract
BACKGROUND: Gastric adenocarcinoma is a heterogenous disease that results from complex interactions between environmental and genetic factors, which may contribute to the disparate outcomes observed between different patient populations. This study aimed to determine whether genomic differences exist in a diverse population of patients by evaluating tumor mutational profiles stratified by race. METHODS: All patients with gastric adenocarcinoma between 2012 and 2016 who underwent targeted next-generation sequencing of cancer genes by the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform were identified. Patient race was categorized as Asian, African American, Hispanic, or Caucasian. Fisher's exact test was used to examine differences in mutation rates between racial designations for the most common mutations identified. The p values in this study were adjusted using the false discovery rate method. RESULTS: The study investigated 595 mutations in 119 patients. The DNA alterations identified included missense mutations (66%), frame-shift deletions (13%), and nonsense mutations (9%). Silent mutations were excluded. The most frequently mutated genes were ARID1A, CDH1, ERBB3, KRAS, PIK3CA, and TP53. Of these, TP53 was the most frequently mutated gene, affecting 50% of patients. The proportion of patients with TP53 mutations differed significantly between races (p = 0.012). The findings showed TP53 mutations for 89% (16/18) of the African American patients, 56% (10/18) of the Asian patients, 43% (9/21) of the Hispanic patients, and 40% (25/62) of the Caucasian patients. CONCLUSIONS: Significantly higher rates of TP53 mutations were identified among the African American patients with gastric adenocarcinoma. This is the first study to evaluate tumor genomic differences in a diverse population of patients with gastric adenocarcinoma.
BACKGROUND:Gastric adenocarcinoma is a heterogenous disease that results from complex interactions between environmental and genetic factors, which may contribute to the disparate outcomes observed between different patient populations. This study aimed to determine whether genomic differences exist in a diverse population of patients by evaluating tumor mutational profiles stratified by race. METHODS: All patients with gastric adenocarcinoma between 2012 and 2016 who underwent targeted next-generation sequencing of cancer genes by the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform were identified. Patient race was categorized as Asian, African American, Hispanic, or Caucasian. Fisher's exact test was used to examine differences in mutation rates between racial designations for the most common mutations identified. The p values in this study were adjusted using the false discovery rate method. RESULTS: The study investigated 595 mutations in 119 patients. The DNA alterations identified included missense mutations (66%), frame-shift deletions (13%), and nonsense mutations (9%). Silent mutations were excluded. The most frequently mutated genes were ARID1A, CDH1, ERBB3, KRAS, PIK3CA, and TP53. Of these, TP53 was the most frequently mutated gene, affecting 50% of patients. The proportion of patients with TP53 mutations differed significantly between races (p = 0.012). The findings showed TP53 mutations for 89% (16/18) of the African American patients, 56% (10/18) of the Asian patients, 43% (9/21) of the Hispanic patients, and 40% (25/62) of the Caucasian patients. CONCLUSIONS: Significantly higher rates of TP53 mutations were identified among the African American patients with gastric adenocarcinoma. This is the first study to evaluate tumor genomic differences in a diverse population of patients with gastric adenocarcinoma.
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