Somatic copy number alterations in gastric adenocarcinomas among Asian and Western patients

PLoS One. 2017 Apr 20;12(4):e0176045. doi: 10.1371/journal.pone.0176045. eCollection 2017.

Abstract

Gastric cancer, a leading worldwide cause of cancer mortality, shows high geographic and ethnic variation in incidence rates, which are highest in East Asia. The anatomic locations and clinical behavior also differ by geography, leading to the controversial idea that Eastern and Western forms of the disease are distinct. In view of these differences, we investigated whether gastric cancers from Eastern and Western patients show distinct genomic profiles. We used high-density profiling of somatic copy-number aberrations to analyze the largest collection to date of gastric adenocarcinomas and utilized genotyping data to rigorously annotate ethnic status. The size of this collection allowed us to accurately identify regions of significant copy-number alteration and separately to evaluate tumors arising in Eastern and Western patients. Among molecular subtypes classified by The Cancer Genome Atlas, the frequency of gastric cancers showing chromosomal instability was modestly higher in Western patients. After accounting for this difference, however, gastric cancers arising in Easterners and Westerners have highly similar somatic copy-number patterns. Only one genomic event, focal deletion of the phosphatase gene PTPRD, was significantly enriched in Western cases, though also detected in Eastern cases. Thus, despite the different risk factors and clinical features, gastric cancer appears to be a fundamentally similar disease in both populations and the divergent clinical outcomes cannot be ascribed to different underlying structural somatic genetic aberrations.

MeSH terms

  • Adenocarcinoma / genetics*
  • Asian Continental Ancestry Group / genetics*
  • DNA Copy Number Variations*
  • European Continental Ancestry Group / genetics*
  • Humans
  • Stomach Neoplasms / genetics*

Grant support

AJB received funding from National Institutes of Health Specialized Programs of Research Excellence grant P50CA127003 (https://grants.nih.gov) and an American Cancer Society Research Scholar Grant (http://www.cancer.org). RAS and RB received funding from the Dana-Farber Cancer Institute/Novartis Drug Discovery Program (http://www.dana-farber.org/, https://www.nibr.com/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.