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Genomic and precision medicine research has afforded notable advances in human cancer treatment, yet applicability to other species remains uncertain. Through whole-exome and transcriptome analyses of 191 spontaneous canine mammary tumors (CMTs) that exhibit the archetypal features of human breast cancers, we found a striking resemblance of genomic characteristics including frequent PIK3CA mutations (43.1%), aberrations of the PI3K-Akt pathway (61.7%), and key genes involved in cancer initiation and progression. We also identified three gene expression-based CMT subtypes, one of which segregated with basal-like human breast cancer subtypes with activated epithelial-to-mesenchymal transition, low claudin expression, and unfavorable disease prognosis. A relative lack of ERBB2 amplification and Her2-enrichment subtype in CMT denoted species-specific molecular mechanisms. Taken together, our results elucidate cross-species oncogenic signatures for a better understanding of universal and context-dependent mechanisms in breast cancer development and provide a basis for precision diagnostics and therapeutics for domestic dogs. Comparison of spontaneous canine cancers and human cancers may illuminate future therapeutic avenues. Here, genomic analyses of these tumors highlights a convergence on PI3K-Akt oncogenic pathways.

Domestic dogs ( Canis lupus familiaris ) serve as valuable translational models for human cancer research due to their biological similarities. Canine mammary tumors (CMTs), frequently diagnosed in female dogs, share various characteristics with human breast cancers. This study investigates the PIK3CA (H1047R) mutation in CMTs using droplet digital PCR (ddPCR) and explores the potential of liquid biopsy for non-invasive detection. We analyzed 80 formalin-fixed, paraffin-embedded (FFPE) CMT tissue samples and compared ddPCR results with next-generation sequencing (NGS) data, achieving high concordance. Plasma and serum samples were also assessed for mutation concordance with tissue results. Our findings indicate a higher frequency of the  PIK3CA (H1047R) mutations in benign and grade I malignant CMTs compared to more aggressive malignancies. The ddPCR assay demonstrated high sensitivity and specificity, with plasma testing showing 78.6% sensitivity and 87.5% specificity, and serum testing showing 66.7% sensitivity and 90.0% specificity. These results highlight the viability of liquid biopsy as a minimally invasive method for monitoring PIK3CA mutations in canine patients. The study suggests that liquid biopsy techniques hold significant promise for improving the early detection and monitoring of canine cancers, warranting further research to refine these methods and explore their applications in canine cancer diagnostics and treatment.

Feline cancer is increasingly recognized as a major cause of mortality, yet data on tumor prevalence and behavior in cats, particularly in non-Western regions, remain limited. This study analyzed a decade of feline tumor data in Korea from 2012 to 2022, focusing on age, breed, and anatomical location as predictors of malignancy. Data were collected from 683 cats, with regression analysis applied to determine significant associations. Older cats exhibited a markedly higher risk of malignancy, particularly in mast cell and mammary tumors. Tumors in the mammary gland and alimentary tract had malignancy rates exceeding 90%, underscoring the need for early detection in these regions. Interestingly, squamous cell carcinoma was rare in the skin, in stark contrast to Western studies, likely reflecting differences in environmental exposure. While breed was not a statistically significant predictor, certain breeds, including Persians and Russian Blues, showed a higher frequency of malignancy. These findings highlight the importance of regional tumor research in cats and the need for larger, multicenter datasets that incorporate environmental, genetic, and lifestyle factors. Understanding these influences will help refine veterinary care and improve cancer treatment outcomes in feline populations.

Spontaneously occurring canine mammary gland tumors share many features with human breast cancer, including biological behavior and histologic features. Compared to transgenic murine model, canine models have advantages including naturally occurring models of human diseases and cancer. In humans, breast cancer is divided into molecular subtypes based on ER, PR, and HER2 expression. In contrast with humans, few studies have evaluated these subtypes in canine mammary gland tumors, including expression of HER2. HER2 expression in canine mammary tissues has been further complicated by controversy regarding the antibody's specificity. This study aimed to investigate c-erbB2 mRNA expression in retrospective formalin-fixed paraffin embedded samples, using RNA in situ hybridization with a novel quantitative assay and to compare this method with immunohistochemistry. Using 48 canine mammary tumor samples and 14 non-neoplastic canine mammary tissues, RNA in situ hybridization was performed with RNAscope® using a canine-specific target gene probe (ERBB2), and quantitative measurement was performed using the housekeeping gene (POLR2A) to calculate the target gene/housekeeping gene ratio. The ratio of ERBB2/POLR2A was quantified using open-source image analysis programs and compared with the immunohistochemistry results. A significant correlation was observed between the HER2 immunohistochemistry score and ERBB2/POLR2A RNA in situ hybridization (P < 0.001). When the HER2 immunohistochemistry score was 3+, significantly higher expression of HER2 mRNA was observed by RNA in situ hybridization. Interestingly, HER2 mRNA was also observed in non-neoplastic mammary tissues by RNA in situ hybridization. This assay potentially facilitates the reliable quantification of mRNA expression levels in retrospective formalin-fixed paraffin-embedded samples. Further studies are required to elucidate the role of HER2 in canine mammary gland tumors and to implement clinical trials in dogs.

Background The domestic dog, Canis lupus familiaris , is a companion animal for humans as well as an animal model in cancer research due to similar spontaneous occurrence of cancers as humans. Despite the social and biological importance of dogs, the catalogue of genomic variations and transcripts for dogs is relatively incomplete. Results We developed CanISO, a new database to hold a large collection of transcriptome profiles and genomic variations for domestic dogs. CanISO provides 87,692 novel transcript isoforms and 60,992 known isoforms from whole transcriptome sequencing of canine tumors ( N  = 157) and their matched normal tissues ( N  = 64). CanISO also provides genomic variation information for 210,444 unique germline single nucleotide polymorphisms (SNPs) from the whole exome sequencing of 183 dogs, with a query system that searches gene- and transcript-level information as well as covered SNPs. Transcriptome profiles can be compared with corresponding human transcript isoforms at a tissue level, or between sample groups to identify tumor-specific gene expression and alternative splicing patterns. Conclusions CanISO is expected to increase understanding of the dog genome and transcriptome, as well as its functional associations with humans, such as shared/distinct mechanisms of cancer. CanISO is publicly available at https://www.kobic.re.kr/caniso/ .

Studies of naturally occurring cancers in dogs, which share many genetic and environmental factors with humans, provide valuable information as a comparative model for studying the mechanisms of human cancer pathogenesis. While individual and small-scale studies of canine cancers are underway, more generalized multi-omics studies have not been attempted due to the lack of large-scale and well-controlled genomic data. Here, we produced reliable whole-exome and whole-transcriptome sequencing data of 197 canine mammary cancers and their matched controls, annotated with rich clinical and biological features. Our dataset provides useful reference points for comparative analysis with human cancers and for developing novel diagnostic and therapeutic technologies for cancers in pet dogs.

The histopathological diagnosis of canine splenic mass lesions is crucial for prognostication. However, thus far, no study has been conducted on the histopathology of canine splenic mass lesions in Republic of Korea. Herein, the prevalence of splenic diseases was analyzed in 137 canine splenic mass lesions via histopathological diagnosis, and the microscopic pattern associated with each disorder was described. Immunohistochemistry was performed for CD31, CD3, PAX5, Iba1, and C-kit for a more accurate diagnosis of splenic tumors. The proportion of non-neoplastic disorders, including nodular hyperplasia (48.2%, n = 66) and hematoma (24.1%, n = 33), was 72.3%. Splenic tumors, including splenic hemangiosarcoma (10.2%, n = 14), splenic lymphoma (nodular and diffuse types, 8.0%, n = 11), splenic stromal sarcoma (7.3%, n = 10), myelolipoma (1.5%, n = 2), and mast cell tumors (0.7%, n = 1), accounted for 27.7% of cases. The results of this study will aid veterinary clinicians in communication with pet owners about prognoses, recommendations for splenectomy, and subsequent histopathological diagnoses. This study will facilitate further investigations with more detailed comparisons of splenic mass lesions between small- and large-breed dogs.

The PI3K/Akt/PTEN axis is one of the most important signaling pathways in tumorigenesis. Recently, mutation of PIK3CA has been highlighted due to the similarities of mutational hotspots in both dogs and humans. PIK3CA H1047R (c.3140A > G) has been discovered as the most common mutational hot spot in canine mammary tumor in recent studies, while the feature of PIK3CA-mutated canine mammary tumor is obscure. Methods: A total of 83 mammary samples classified as normal (n = 13), adenoma (n = 25), low-grade carcinoma (n = 21), and high-grade carcinoma (n = 24) were included in this study. Genomic DNA from each sample was extracted, amplified by conventional PCR, and analyzed through Sanger sequencing. Analysis for the expression of PIK3CA, Akt, p-Akt, and PTEN was performed by immunohistochemistry, and of Akt2 by RNA in situ hybridization. Results: PIK3CA H1047R mutation was detected in 14.3% (10/70) of tumor samples. Dysregulation of p-Akt, Akt2, and PTEN was observed in mammary tumor samples, but only PTEN dysregulation was associated with PIK3CA H1047R mutation. Conclusions: The present study showed that dysregulation of components in the PI3K/Akt/PTEN pathway is a feature of canine mammary tumors, but this dysregulation is not directly correlated to the PIK3CA H1047R mutation except for PTEN expression.

The identification of efficient and sensitive biomarkers for non-invasive tests is one of the major challenges in cancer diagnosis. To address this challenge, metabolomics is widely applied for identifying biomarkers that detect abnormal changes in cancer patients. Canine mammary tumors exhibit physiological characteristics identical to those in human breast cancer and serve as a useful animal model to conduct breast cancer research. Here, we aimed to provide a reliable large-scale metabolite dataset collected from dogs with mammary tumors, using proton nuclear magnetic resonance spectroscopy. We identified 55 metabolites in urine samples from 20 benign, 87 malignant, and 49 healthy control subjects. This dataset provides details of mammary tumor-specific metabolites in dogs and insights into cancer-specific metabolic alterations that share similar molecular characteristics. Measurement(s) Metabolite Technology Type(s) 1H nuclear magnetic resonance spectroscopy Factor Type(s) Age • Breeds • Sex • ER status • HER2 status • Histological grade • Neutral status Sample Characteristic - Organism Canis lupus familiaris

Background Given the active research on targeted therapy using tyrosine kinase (TK) inhibitors (TKIs) in the field of oncology, further studies have recently been conducted to evaluate their use in autoimmune disorders. Based on immunological investigations, previous studies have suggested that granulomatous meningoencephalomyelitis (GME) and necrotizing encephalomyelitis (NE) are similar to multiple sclerosis (MS), which is a human autoimmune demyelinating central nervous system disease. Objectives Considering this perspective, we hypothesized that canine GME and NE have significant expression of one or more TKs, which are associated with human MS pathogenesis. Methods To determine the possible use of conventional multi‐targeted TKIs as a treatment for canine GME and NE, we characterized the immunohistochemical expression of platelet‐derived growth factor receptor (PDGFR)‐α, PDGFR‐ß, vascular endothelial growth factor receptor (VEGFR)‐2, c‐Abl and c‐Kit in GME and NE samples. Results Histological samples from four dogs with GME and three with NE were retrieved. All samples stained positive for PDGFR‐ß (7/7 [100%]). PDGFR‐α and c‐Kit were expressed in 3/7 (42.8%) samples each. c‐Abl was identified in 2/7 (28.5%) samples; no sample showed VEGFR‐2 (0%) expression. Co‐expression of TKs was identified in 6/7 (85.7%) dogs. Conclusions All samples were positive for at least one or more of PDGFR‐α, PDGFR‐ß, c‐Kit and c‐Abl, which are known as the target TKs of conventional multi‐targeted TKIs. Their presence does suggest that these TKs may play a role in the pathogenesis of GME and NE. Therefore, multi‐targeted TKIs may provide benefits in the treatment of canine GME and NE by suppressing the activity of these TKs. All GME and NE samples expressed one or more of the known targets of conventional multi‐targeted TKIs, suggesting that these kinases may play a role in the pathogenesis and development of GME and NE. Furthermore, multi‐targeted therapy with TKIs may provide benefits in the treatment of canine GME and NE by suppressing the activity of these TKs.