SCIENCE@home

Genomic analyses identify 15 susceptibility loci and reveal HDAC2, SOX2-OT, and IGF2BP2 in a naturally-occurring canine model of gastric cancer

S. Cook,S. Hugen,J. Hayward,T. Famula,J. M. Belanger,Elizabeth McNiel,H. Fieten,Anita M Oberbauer,Peter A Leegwater,E. Ostrander,P. Mandigers,Jacquelyn M. Evans

Published 2024 in bioRxiv

ABSTRACT

Gastric cancer (GC) is the fifth most common human cancer worldwide, but the genetic etiology is largely unknown. We performed a Bayesian genome-wide association study and selection analyses in a naturally-occurring canine model of GC, the Belgian Tervuren and Sheepdog breeds, to elucidate underlying genetic risk factors. We identified 15 loci with over 90% predictive accuracy for the GC phenotype. Variant filtering revealed germline putative regulatory variants for the EPAS1 (HIF2A) and PTEN genes and a coding variant in CD101. Although closely related to Tervuren and Sheepdogs, Belgian Malinois rarely develop GC. Across-breed analyses uncovered protective haplotypes under selection in Malinois at SOX2-OT and IGF2BP2. Among Tervuren and Sheepdogs, HDAC2 putative regulatory variants were present at comparatively high frequency and were associated with GC. Here, we describe a complex genetic architecture governing GC in a dog model, including genes such as PDZRN3, that have not been associated with human GC.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-100 of 159 references · Page 1 of 2

12
Next

CITED BY