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.
ABSTRACT
The postmortem examination can be used as a means of quality control for clinical diagnoses. A retrospective study on 300 dogs and cats that had been admitted to a small animal intensive care unit was performed comparing the clinical and postmortem findings, using the Modified Goldman criteria. All patient files were reevaluated for clinical diagnoses and all postmortem material was reevaluated for pathological diagnoses. After this, the Modified Goldman criteria were applied to score the discrepancies between them, and factors associated with the occurrence of an undiagnosed major unexpected finding were analyzed. The postmortem examination revealed additional findings in 65% of the cases. Major discrepancies, defined as those affecting treatment and possibly outcome of the patient, were present in 21.3% of the cases. The most frequently missed diagnoses detected at necropsy were pneumonia of various etiologies, meningitis/meningoencephalitis, myocarditis and generalized vasculitis. A shorter ICU stay was associated with increased odds of a major discrepancy. Conditions affecting the urinary or gastrointestinal system were negatively associated with major discrepancy.
Subject(s)
Cat Diseases , Dog Diseases , Animals , Cats , Dogs , Retrospective Studies , Cat Diseases/diagnosis , Cause of Death , Dog Diseases/diagnosis , Diagnostic Errors/veterinary , Critical CareABSTRACT
Gastric carcinoma is generally considered to be a rare disease in dogs, carrying a grave prognosis. However, in the Tervueren and Groenendael varieties of the Belgian Shepherd dog breed, the disease is highly prevalent. While histopathology is the gold standard for diagnosing gastric carcinoma, there is no general consensus on the methods for histological classification in these cases. Biopsies of a group of 61 dogs with confirmed gastric carcinoma (45 Tervueren and 16 Groenendael) were examined and classified according to World Health Organization (WHO) and Laurén classifications. Kaplan-Meier curves were used to compare survival between the different subtypes and simple and multiple linear regression were used to analyse the association between age of onset and breed variant, sex, neuter status, location of the tumour, inflammation score, and Laurén and WHO classifications. Mean age at diagnosis was significantly different in Groenendael (10.1 ± 2.01) and Tervueren dogs (8.5 ± 1.90). The Laurén classification resulted in 29 (48%) diffuse- and 32 (52%) intestinal-type tumours. Applying the WHO classification resulted in 30 (49%) tubular carcinoma growth patterns and 31 (51%) others. Median survival time was significantly reduced for the diffuse type as compared to the intestinal type according to the Laurén classification, with the same median survival time results for tubular compared to non-tubular subtypes according to the WHO classification (median survival time of 61 vs. 182 days, respectively). Using the WHO and Lauren classification on tumour biopsies may help the practising clinician in the prognostication of gastric carcinoma in Tervueren and Groenendael dogs.