Cross‐species analysis of the canine and human bladder cancer transcriptome and exome

Abstract

We investigated the correspondence between transcriptome and exome alterations in canine bladder cancer and the correspondence between these alterations and cancer-driving genes and transcriptional alterations in human bladder cancer. We profiled canine bladder tumors using mRNA-seq and exome-seq in order to investigate the similarity of transcriptional alterations in bladder cancer, in humans and canines, at the levels of gene functions, pathways, and cytogenetic regions. We found that the transcriptomes of canine and human bladder cancer are remarkably similar at the functional and pathway levels. We demonstrated that canine bladder cancer involves coordinated differential expression of genes within cytogenetic bands, and that these patterns are consistent with those seen in human bladder cancer. We found that genes that are mutated in canine bladder cancer are more likely to be transcriptionally downregulated than non-mutated genes, in the tumor. Finally we report three novel mutations (FAM133B, RAB3GAP2, and ANKRD52) for canine bladder cancer.

A comparative meta and in silico analysis of differentially expressed genes and proteins in canine and human bladder cancer

“…We selected three previous studies that evaluated the transcriptome (RNA-seq) of canine bladder carcinoma, with the data sets available online at NCBI short-read archive (SRA) under BioProject ID PRJNA559406 (Parker et al, 2020), GEO database (ref: GSE24152) (Dhawan et al, 2018) or available at the DDBJ Sequenced Read Archive repository (http://trace.ddbj.nig.ac.jp/dra/index_e.html) with accession number DRA005844). Besides that, we also included one manuscript evaluating the transcriptome of canine bladder cancer using microarray data (Dhawan et al, 2015) and one manuscript that performed both mRNA-seq and exome-seq (Ramsey et al 2017). For both studies (Dhawan et al 2015 and Ramsey et al 2017) mRNA data were obtained in supplementary information.…”

“…Besides that, we also included one manuscript evaluating the transcriptome of canine bladder cancer using microarray data (Dhawan et al, 2015) and one manuscript that performed both mRNA-seq and exome-seq (Ramsey et al 2017). For both studies (Dhawan et al 2015 and Ramsey et al 2017) mRNA data were obtained in supplementary information.…”

“…Transitional cell carcinoma (TCC), also called urothelial carcinoma, is the most common bladder cancer in both humans and dogs, sharing clinical, pathological and molecular alterations (Dhawan et al, 2018, Maeda et al, 2018, Ramsey et al, 2017). In the United States, it is expected 81.400 new cases and 17.980 bladder cancer-related deaths (Siegel et al, 2020).…”

Comparative oncology: Integrating human and veterinary medicine

“…Canine TCC closely mimics the human invasive bladder cancer in various features like the microscopic features, biological behaviour and response to treatment (Knapp et al, 2000). Canine and human bladder cancers have been found very similar at the level of transcriptome alterations (Ramsey et al, 2017). Cyclooxygenase-2 (Cox-2) has been found to be overexpressed in both human and canine bladder cancer (Mohammed 1999, Shirahama 2000Cekanova et al, 2013).…”

A domestic cat whole exome sequencing resource for trait discovery

“…The domestic dog with a large number of isolated breeds are an important genetic resource for cancer studies, and WES has shown similar oncogene variant patterns that enable comparative analysis in humans 21,22 . On the other hand, an analysis of human and canine bladder cancer using WES data identified novel mutations in FAM133B , RAB3GAP2 , and ANKRD52 that are unique to canine bladder cancer suggesting biological differences in origin 23 .…”