Hispanic/Latino gastric adenocarcinoma patients have distinct molecular profiles including a high rate of germline cdh1 mutations

Sam C. Wang, Yunku Yeu, Suntrea T.G. Hammer, Shu Xiao, Min Zhu, Changjin Hong, Lynn Y. Yoon, Ibrahim Nassour, Jeanne Shen, Deepak Agarwal, Scott I. Reznik, John C. Mansour, Adam C. Yopp, Hao Zhu, Tae Hyun Hwang, Matthew R. Porembka

Research output: Contribution to journalArticlepeer-review

Abstract

Hispanic/Latino patients have a higher incidence of gastric cancer and worse cancer-related outcomes as compared to patients of other backgrounds. Whether there is a molecular basis for these disparities is unknown, as very few Hispanic/Latino patients were included in previous studies. We performed a large, integrated genomic analysis of gastric cancer samples from Hispanic/Latino patients. Whole-exome sequencing (WES) and RNA sequencing were performed on 57 Hispanic/Latino gastric cancer patient samples. Germline analysis was conducted on 83 patients. Functional testing of CDH1 germline mutations was performed in Chinese hamster ovary cells. Tumors from Hispanic/Latino patients were significantly enriched for the genomically-stable subtype (as defined by The Cancer Genome Atlas), compared to Asians and Whites (65% vs 21% vs 20%, P < 0.001). Transcriptomic analysis identified molecular signatures that were prognostic. Of the 43 Hispanic/Latino patients with diffuse-type gastric cancer, 7 (16%) had germline mutations in CDH1. Mutation carriers were significantly younger than non-carriers (41 vs 50 years, P < 0.05). E-cadherin expression was reduced in 5 of 6 mutation carrier tumor samples available for analysis. In silico algorithms predicted 5 variants were deleterious. For the two variants that were predicted to be benign, we demonstrated that the mutations conferred increased migratory capability, suggesting pathogenicity. Hispanic/Latino gastric cancer patients possess unique genomic landscapes. This includes a high rate of CDH1 germline mutations that may partially explain their aggressive clinical phenotypes. Individualized screening, genetic counseling, and treatment protocols based on patient ethnicity and race may be necessary.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Sep 11 2019

Keywords

  • Cancer disparity
  • Cancer genomics
  • CDH1
  • E-cadherin
  • Gastric cancer
  • Hispanic
  • Latino

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'Hispanic/Latino gastric adenocarcinoma patients have distinct molecular profiles including a high rate of germline cdh1 mutations'. Together they form a unique fingerprint.

Cite this