Unique genomic alterations and microbial profiles identified in patients with gastric cancer of African, European, and Asian Ancestry: A novel path for precision oncology Conference Paper


Authors: Abate, M.; Walch, H.; Arora, K.; Vanderbilt, C. M.; Fei, T.; Drebin, H.; Shimada, S.; Maio, A.; Kemel, Y.; Stadler, Z. K.; Schmeltz, J.; Sihag, S.; Ku, G. Y.; Gu, P.; Tang, L.; Vardhana, S.; Berger, M. F.; Brennan, M. F.; Schultz, N. D.; Strong, V. E.
Title: Unique genomic alterations and microbial profiles identified in patients with gastric cancer of African, European, and Asian Ancestry: A novel path for precision oncology
Conference Title: 143rd Annual Meeting of the American Surgical Association (ASA)
Abstract: Objective: Here, we characterize differences in the genetic and microbial profiles of GC in patients of African (AFR), European, and Asian ancestry. Background: Gastric cancer (GC) is a heterogeneous disease with clinicopathologic variations due to a complex interplay of environmental and biological factors, which may affect disparities in oncologic outcomes. Methods: We identified 1042 patients with GC with next-generation sequencing data from an institutional Integrated Mutation Profiling of Actionable Cancer Targets assay and the Cancer Genomic Atlas group. Genetic ancestry was inferred from markers captured by the Integrated Mutation Profiling of Actionable Cancer Targets and the Cancer Genomic Atlas whole exome sequencing panels. Tumor microbial profiles were inferred from sequencing data using a validated microbiome bioinformatics pipeline. Genomic alterations and microbial profiles were compared among patients with GC of different ancestries. Results: We assessed 8023 genomic alterations. The most frequently altered genes were TP53, ARID1A, KRAS, ERBB2, and CDH1. Patients of AFR ancestry had a significantly higher rate of CCNE1 alterations and a lower rate of KRAS alterations (P < 0.05), and patients of East Asian ancestry had a significantly lower rate of PI3K pathway alterations (P < 0.05) compared with other ancestries. Microbial diversity and enrichment did not differ significantly across ancestry groups (P > 0.05). Conclusions: Distinct patterns of genomic alterations and variations in microbial profiles were identified in patients with GC of AFR, European, and Asian ancestry. Our findings of variation in the prevalence of clinically actionable tumor alterations among ancestry groups suggest that precision medicine can mitigate oncologic disparities. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Keywords: genetics; mutation; pathology; phosphatidylinositol 3 kinase; genomics; protein p21; proto-oncogene proteins p21(ras); stomach neoplasms; stomach tumor; personalized medicine; phosphatidylinositol 3-kinases; microbiome; humans; human; precision medicine; cancer disparities; ethnicities
Journal Title Annals of Surgery
Volume: 278
Issue: 4
Conference Dates: 2023 Apr 20-22
Conference Location: Toronto, Canada
ISBN: 0003-4932
Publisher: Lippincott Williams & Wilkins  
Date Published: 2023-10-01
Start Page: 506
End Page: 518
Language: English
DOI: 10.1097/sla.0000000000005970
PUBMED: 37436885
PROVIDER: scopus
PMCID: PMC10527605
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Vivian E. Strong -- Source: Scopus
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MSK Authors
  1. Murray F Brennan
    1059 Brennan
  2. Geoffrey Yuyat Ku
    230 Ku
  3. Zsofia Kinga Stadler
    387 Stadler
  4. Laura Hong Tang
    447 Tang
  5. Vivian Strong
    264 Strong
  6. Michael Forman Berger
    764 Berger
  7. Nikolaus D Schultz
    486 Schultz
  8. Yelena Kemel
    103 Kemel
  9. Santosha Adipudi Vardhana
    102 Vardhana
  10. Smita Sihag
    96 Sihag
  11. Ping Gu
    17 Gu
  12. Henry Stuart Walch
    100 Walch
  13. Anna Maio
    35 Maio
  14. Kanika Suresh Arora
    27 Arora
  15. Miseker Eshetu Abate
    11 Abate
  16. Shoji Shimada
    11 Shimada
  17. Teng Fei
    40 Fei
  18. Harrison Martin Drebin
    14 Drebin