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

• Published in: PloS one 2015-07, Vol.10 (7), p.e0131280
• Main Authors: Hennecke, Silvia, Beck, Julia, Bornemann-Kolatzki, Kirsten, Neumann, Stephan, Murua Escobar, Hugo, Nolte, Ingo, Hammer, Susanne Conradine, Hewicker-Trautwein, Marion, Junginger, Johannes, Kaup, Franz-Josef, Brenig, Bertram, Schütz, Ekkehard
• Format: Article
• Language: English
• Subjects: Animals; Benign; Breast cancer; c-Myc protein; Cancer; Cancer genetics; Carcinogenesis; Carcinogens; Carcinoma; Cell growth; Chromosome deletion; Chromosomes; Copy number; Deoxyribonucleic acid; DNA; Dogs; Female; Gene Deletion; Genes; Genomes; Hematology; Immunohistochemistry; Leukocytes; Mammary Neoplasms, Animal - genetics; Mastectomy; Medical research; Molecular Chaperones - genetics; Myc protein; Oncology; Palliative care; Pathology; Prevalence studies (Epidemiology); Protein Subunits - genetics; Rodents; Thyroid gland; Tissues; Tumor suppressor genes; Tumors; Veterinary medicine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0131280

A 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. Droplet 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. The 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