ICCFGG 2022
#12 Genomic characterization of canine carcinoma of the prostate shows similarity to canine urothelial carcinoma
Claire Wiley1 , Catherine F. Wise2, Rachael Thomas1,4 Gregory Krane1,3, Janice Harvey3, Valerie Ortiz1, Matthew Breen1,4,5 cawiley2@ncsu.edu
1Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA; 2Department of Toxicology, North Carolina State University, Raleigh, North Carolina, USA; 3National Institute of Environmental Health Sciences, Durham, North Carolina, USA; 4Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA; 5Duke Cancer Institute, Durham, North Carolina, USA Carcinomas affecting the canine prostate (PC) represent an aggressive cancer with a shorter median survival time than other carcinomas of the urinary tract, despite similar treatment. Histologic characterization is often indistinguishable from urothelial carcinoma (UC), suggesting that the majority of PC is in fact UC. The grave prognosis suggests that PC may warrant a separate classification. Using whole exome sequencing (WES) and comparative genomic hybridization (oaCGH), this study aimed to perform a genomic characterization of canine PC and to compare findings to canine UC. Twenty-nine PC tumor samples from client-owned dogs were characterized by two veterinary pathologists. Genomic DNA isolation was performed on tumor-enriched regions and matched normal tissues for WES and oaCGH. When segregated based on clinical or histologic features, no clear patterns of aberrations were observed. The previously identified BRAF V595E mutation was present in 83% of canine PC tumors, a prevalence comparable to UC. Genome-wide copy number profiling using oaCGH revealed that 66% of PC shared a previously published profile prevalent in UC, consisting of gains of chromosome 13 and 36 and loss of chromosome 19. These genomic similarities of PC to UC confirm the suspicion that these diseases are indistinguishable. Overall, canine PC showed clinical, genomic, and histologic heterogeneity, which is similar to findings in human PC. The second most frequent variant was present in only 28% of PC tumors, suggesting a precision medicine approach may be necessary to improve survival. #13 Identification of a novel locus associated with Addison’s Disease in Standard Poodles Elizabeth A. Greif1 , Steven G. Friedenberg1, and Leigh Anne Clark1 egreif@g.clemson.edu 1Clemson University, Clemson South Carolina, USA Addison’s disease is a complex autoimmune disease of people and dogs in which the outer layers of the adrenal glands are destroyed, leading to low levels of serum cortisol and aldosterone. Nonspecific symptoms often delay diagnosis and affected individuals require lifelong, costly hormone replacement therapy for survival. Susceptibility alleles of the major histocompatibility complex have been identified in both people and dogs, but it is clear that additional genetic factors are involved in disease pathogenesis. Standard Poodles have a uniquely high disease prevalence, presenting a model system for the identification of genetic risk factors. We generated genome-wide single nucleotide polymorphism (SNP) profiles for 287 carefully phenotyped Standard Poodles
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