Dataset Information

Transcriptomic Profile of Canine Mammary Ductal Carcinoma.

ABSTRACT: Dogs can be excellent models for spontaneous studies about breast cancers, presenting similarities in clinical behavior and molecular pathways of the disease. Thus, analyses of the canine transcriptome can identify deregulated genes and pathways, contributing to the identification of biomarkers and new therapeutic targets, benefiting humans and animals. In this context, this study aimed to determine the transcriptional profile of canine mammary ductal carcinoma and contribute to the clarification of the importance of deregulated molecules in the molecular pathways involved in the disease. Therefore, we used mammary ductal carcinoma tissue samples and non-tumor mammary tissue from the radical mastectomy of six female dogs. Sequencing was performed on the NextSeq-500 System platform. A comparison of carcinoma tissue and normal tissue revealed 633 downregulated and 573 upregulated genes, which were able to differentiate the groups by principal component analysis. Gene ontology analysis indicated that inflammatory, cell differentiation and adhesion, and extracellular matrix maintenance pathways were mainly deregulated in this series. The main differentially expressed genes observed in this research can indicate greater disease aggressiveness and worse prognosis. Finally, the study of the canine transcriptome indicates that it is an excellent model to generate information relevant to oncology in both species.

SUBMITTER: Santos DB

PROVIDER: S-EPMC10049542 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Transcriptomic Profile of Canine Mammary Ductal Carcinoma.

Santos Driéle B DB Fernandez Geysson J GJ Pardini Luciana M C LMC Pardini Maria Inês M C MIMC Ferrasi Adriana C AC

International journal of molecular sciences 20230308 6

Dogs can be excellent models for spontaneous studies about breast cancers, presenting similarities in clinical behavior and molecular pathways of the disease. Thus, analyses of the canine transcriptome can identify deregulated genes and pathways, contributing to the identification of biomarkers and new therapeutic targets, benefiting humans and animals. In this context, this study aimed to determine the transcriptional profile of canine mammary ductal carcinoma and contribute to the clarificatio ...[more]

PMID: 36982287

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Project description:The incidence and prevalence of paraneoplastic glomerulopathy, especially associated with carcinoma, are a matter of debate and the causal link between cancer and glomerular diseases remains unclear. The aim of this study was to evaluate renal biopsies of selected bitches with spontaneous mammary gland carcinoma. We hypothesized that dogs with mammary carcinomas would show histologic evidence of glomerular pathology. A prospective study was performed in dogs with naturally occurring mammary carcinoma that were undergoing tumor resection and ovariohysterectomy. We evaluated renal biopsies of 32 bitches with spontaneous mammary gland carcinoma and 11 control dogs without mammary gland neoplasia. Samples were obtained from the left kidney and the biopsy material was divided for light microscopy (LM), immunofluorescence (IF) and transmission electron microscopy (TEM). Light microscopy abnormalities were identified in 78.1% of dogs with mammary carcinoma (n = 25) and in none of the dogs in the control group. Focal glomerular mesangial matrix expansion was the most common alteration (n = 15, 60.0%), but mesangial cell proliferation (n = 9, 36.0%) and focal segmental glomerulosclerosis (n = 9, 36.0%), synechiae (n = 7, 28.0%), and globally sclerotic glomeruli (n = 6, 24.0%) were also frequent in dogs with malignancy. Immunofluorescence microscopy revealed strong IgM staining was demonstrated in 64.3% (n = 18) of carcinoma dogs. Transmission electron microscopy from dogs with carcinoma revealed slight changes, the most frequent of which was faint sub-endothelial and mesangial deposits of electron-dense material (78%). Mesangial cell interpositioning and segmental effacement of podocyte foot processes were identified in some specimens (45%). Changes in the glomerulus and proteinuria are common in dogs with naturally occurring mammary carcinoma and this condition appears to provide an excellent large animal model for cancer-associated glomerulopathy in humans.

Project description:BackgroundBreast cancer (BC) is the most common cancer in women. Likewise, canine mammary tumors (CMT) represent the most common cancer in intact female dogs and develop in the majority spontaneously. Similarities exist in clinical presentation, histopathology, biomarkers, and treatment. However, CMT subtype-specific genomic background is less investigated. Here, we assess the genetic etiology of two histomorphological (HM) subtypes with BC counterparts, the CMT invasive ductal simple solid carcinoma (SC) and comedocarcinoma (CC), and compare the results with BC data.MethodsGroups of 11-13 transformed ductal luminal epithelial cells were laser-capture microdissected from snap-frozen invasive mammary SC and CC subtypes of one intact female dog. HM unaffected lobular luminal epithelial cells were controls. Single-cell whole genome libraries were generated using PicoPLEX and sequenced to compare the subtypes' somatic coding variant landscapes with each other and with BC data available in COSMIC-CGC and KEGG. Furthermore, HM and immunohistochemical (IHC) subtype characteristics were compared with the genomic results.ResultsThe CC had six times more variants than the SC. The SC showed variants in adherens junction genes and genes of the MAPK, mTOR and NF-kappa-B signaling pathways. In the CC, the extracellular matrix (ECM) receptor interaction, cell adhesion, PI3K-Akt and cGMP-PKG pathways were enriched, reflecting the higher cellular malignancy. Affected pathways in both CMT subtypes overlapped with BC pathways in KEGG. Additionally, we identified ATP6V1C2, GLYATL3, CARMIL3, GATAD2B, OBSCN, SIX2, CPEB3 and ZNF521 as potential new subtype-distinct driver genes. Furthermore, our results revealed biomarker alterations in IHC in the basal/myoepithelial cell layer without respective genetic mutations, suggesting changes to their complex signaling pathways, disturbed regulative feedback loops or other silencing mechanisms.ConclusionsThis study contributes to understanding the subtype-specific molecular mechanisms in the canine mammary invasive ductal simple SC and CC, and revealed subtype-specific molecular complexity for phenotypically similar characteristics. Several affected genes and signaling pathways overlapped with BC indicating the potential use of CMT as model for BC. Our findings emphasize the need for thorough characterization of cancer specimens with respect to translational cancer research, but also how insight into tumor heterogeneity will be crucial for the development of targeted prognostics and therapeutic interventions.

Dataset Information

Transcriptomic Profile of Canine Mammary Ductal Carcinoma.

Publications

Transcriptomic Profile of Canine Mammary Ductal Carcinoma.

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