Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors

Abstract

BackgroundA somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors.MethodsDroplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32). Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores ≤ -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry.ResultsThe deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9) showed the highest frequency of the deletion (67%) and those malignomas without microscopical high fraction of benign tissue (n = 71) had a 32% frequency (p<0.01 vs. benign samples). The Ki-67 score was found to be significantly higher (p<0.05) in the PFDN5-deleted group compared to malignant tumors without the deletion.ConclusionsA somatic deletion of the PFDN5 gene is recurrently present in canine mammary cancer, supporting a potential role in carcinogenesis. The association of this deletion with higher Ki-67 indicates an increased proliferation rate and thus a link to tumor aggressiveness can be hypothesized. The confirmation of earlier results warrants further studies on PFDN5 as cancer-driver gene.

Multiplex Gene Expression Profiling of 16 Target Genes in Neoplastic and Non-Neoplastic Canine Mammary Tissues Using Branched-DNA Assay

“…However, it has been shown to be a tumor suppressor candidate in leukemia and tongue cancer [ 38 ]. The outcomes herein revealed higher expression in non-neoplastic tissue, suggesting it as a potential tumor marker just as demonstrated by Hennecke and colleagues [ 15 ]. Moreover, a previous study demonstrated that PFDN5 was recurrently deleted in CMT [ 26 ].…”

“…The gene expression profile of the mammary tumor in dogs is, to date, not well characterized and the use of tumor markers is still for research purposes only [ 15 ]. The analysis and differentiation of the mammary tumors is the basis for pathogenesis, diagnosis, prognosis, new therapy options, and good breed hygiene practice.…”

“…In contrast to the human counterpart, the use of mammary tumor biomarkers in canines is still restricted to research purposes [ 14 , 15 ]. Expression of BRCA1 and BRCA2 in CMT was analyzed and it was found to be associated with an increased mammary tumor risk in English Springer Spaniels (ESS) [ 16 ].…”

“…A possible influence of those genes in tumor development is also suggested in other studies [ 17 , 18 , 19 , 20 ]. Further targets of those analyzed herein have also been investigated in CMT such as TP53 [ 21 , 22 ], PTEN [ 23 , 24 , 25 , 26 , 27 ], PFDN5 [ 15 , 26 ], MYC [ 27 ], HER2 [ 28 ], and MCL1 [ 29 ] associating their expression patterns with the development of CMT.…”

Hormone Receptor Expression Analyses in Neoplastic and Non-Neoplastic Canine Mammary Tissue by a Bead Based Multiplex Branched DNA Assay: A Gene Expression Study in Fresh Frozen and Formalin-Fixed, Paraffin-Embedded Samples

“…Nevertheless, other hormone receptors such as prolactin receptor (PRLR) or growth hormone receptor (GHR) have been evaluated in human breast cancer [ 10 – 11 ]. As approximately 50% of mammary gland tumors in dogs appear to be malignant [ 12 – 13 ], the detection of novel canine tumor markers with a value for prognosis or targeted therapy are the focus of research [ 14 – 19 ]. Therefore, in the present study, the gene expression of ESR1, PGR, PRLR and GHR were analyzed simultaneously to compare their distribution in canine mammary tissue.…”