Genomic Analysis of Lymphoma Risk in Bullmastiff Dogs

Sally A Mortlock; Monica C Asada; Pamela Xing Yi Soh; Wei-Tse Hsu; Carol Lee; Peter F Bennett; Rosanne M Taylor; Mehar S Khatkar; Peter Williamson

doi:10.3390/vetsci10120703

Genomic Analysis of Lymphoma Risk in Bullmastiff Dogs

Vet Sci. 2023 Dec 14;10(12):703. doi: 10.3390/vetsci10120703.

Authors

Affiliations

¹ Sydney School of Veterinary Science, Faculty of Science, The University of Sydney, Camperdown, NSW 2006, Australia.
² School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Camperdown, NSW 2006, Australia.
³ School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia.
⁴ School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, SA 5371, Australia.

Abstract

Lymphoma is the most common haematological malignancy affecting dogs and has a high incidence in the Bullmastiff breed. The aim of this study was to identify risk loci predisposing this breed to the disease. The average age of lymphoma diagnosis in 55 cases was less than 6 years, similar to the median age of 64 cases from our clinical and pathology databases. When fine-scale population structure was explored using NETVIEW, cases were distributed throughout an extended pedigree. When genotyped cases (n = 49) and dogs from the control group (n = 281) were compared in a genome-wide association analysis of lymphoma risk, the most prominent associated regions were detected on CFA13 and CFA33. The top SNPs in a 5.4 Mb region on CFA13 were significant at a chromosome-wide level, and the region was fine-mapped to ~1.2 Mb (CFA13: 25.2-26.4 Mb; CanFam3.1) with four potential functional candidates, including the MYC proto-oncogene bHLH transcription factor (MYC) and a region syntenic with the human and mouse lncRNA Pvt1 oncogene (PVT1). A 380 Kb associated region at CFA33: 7.7-8.1 Mb contained the coding sequence for SUMO specific peptidase7 (SENP7) and NFK inhibitor zeta (NFKBIZ) genes. These genes have annotations related to cancer, amongst others, and both have functional links to MYC regulation. Genomic signatures identified in lymphoma cases suggest that increased risk contributed by the regions identified by GWAS may complement a complex predisposing genetic background.

Keywords: Bullmastiff; GWAS; canine; lymphoma.

Grants and funding

This work was supported by funds from the Australian Canine Research Foundation (PW), the Sarah and Ann Payten Cancer Research Fund of the Faculty of Veterinary Science, University of Sydney (PW), and by the Maple Simmons Donation (PW&SM). SM, and PXYS were recipients of an Australian Postgraduate Award provided by the Australian Federal Government. WTH was the recipient of a University of Sydney International Scholarship and a Taiwan Government Scholarship to Study Abroad.