Rates of TP53 mutation are significantly elevated in African American patients with gastric cancer Journal Article

Authors: van Beek, E. J. A. H.; Hernandez, J. M.; Goldman, D. A.; Davis, J. L.; McLaughlin, K.; Ripley, R. T.; Kim, T. S.; Tang, L. H.; Hechtman, J. F.; Zheng, J.; Capanu, M.; Schultz, N.; Hyman, D. M.; Ladanyi, M.; Berger, M. F.; Solit, D. B.; Janjigian, Y. Y.; Strong, V. E.
Article Title: Rates of TP53 mutation are significantly elevated in African American patients with gastric cancer
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. © 2018, Society of Surgical Oncology.
Keywords: adult; controlled study; human tissue; aged; unclassified drug; major clinical study; frameshift mutation; missense mutation; cancer patient; gene targeting; protein; retrospective study; protein p53; uvomorulin; dna; epidermal growth factor receptor 3; k ras protein; stomach adenocarcinoma; tumor gene; race difference; fisher exact test; african american; nonsense mutation; caucasian; race; hispanic; asian; retinoblastoma binding protein 2; next generation sequencing; very elderly; human; male; female; article; pik3ca protein
Journal Title: Annals of Surgical Oncology
Volume: 25
Issue: 7
ISSN: 1068-9265
Publisher: Springer  
Date Published: 2018-07-01
Start Page: 2027
End Page: 2033
Language: English
DOI: 10.1245/s10434-018-6502-x
PROVIDER: scopus
PUBMED: 29725898
Notes: Article -- Export Date: 2 July 2018 -- Source: Scopus
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MSK Authors
  1. David Solit
    435 Solit
  2. Marinela Capanu
    209 Capanu
  3. Yelena Yuriy Janjigian
    146 Janjigian
  4. Marc Ladanyi
    870 Ladanyi
  5. David Hyman
    187 Hyman
  6. Laura Hong Tang
    327 Tang
  7. Vivian Strong
    148 Strong
  8. Michael Forman Berger
    386 Berger
  9. Teresa Sora Kim
    23 Kim
  10. Nikolaus D Schultz
    202 Schultz
  11. Debra Alyssa Goldman
    94 Goldman
  12. Jaclyn Frances Hechtman
    104 Hechtman
  13. Jeremy Lee Davis
    5 Davis
  14. Jian Ying Zheng
    14 Zheng