title: Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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<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.
  
  
  CONCLUSIONS
  A 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.
authors.affiliation: Institute of Veterinary Medicine, Georg-August-University Goettingen, Goettingen, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Hennecke
authors.affiliation: Chronix Biomedical, Goettingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Beck
authors.affiliation: Chronix Biomedical, Goettingen, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bornemann-Kolatzki
authors.affiliation: Institute of Veterinary Medicine, Georg-August-University Goettingen, Goettingen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Neumann
authors.affiliation: Small Animal Clinic, University of Veterinary Medicine Hannover, Hannover, Germany; Hematology Oncology and Palliative Medicine, ClinicIII, University of Rostock, Rostock, Germany.
authors.forename: Hugo
authors.initials: H
authors.lastname: Murua Escobar
authors.affiliation: Small Animal Clinic, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Nolte
authors.affiliation: Small Animal Clinic, University of Veterinary Medicine Hannover, Hannover, Germany; Hematology Oncology and Palliative Medicine, ClinicIII, University of Rostock, Rostock, Germany.
authors.forename: Susanne Conradine
authors.initials: SC
authors.lastname: Hammer
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Hewicker-Trautwein
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Junginger
authors.affiliation: German Primate Center, Goettingen, Germany.
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Kaup
authors.affiliation: Institute of Veterinary Medicine, Georg-August-University Goettingen, Goettingen, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Brenig
authors.affiliation: Institute of Veterinary Medicine, Georg-August-University Goettingen, Goettingen, Germany; Chronix Biomedical, Goettingen, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Schütz
mesh_terms: D000818:Animals; D004285:Dogs; D005260:Female; D017353:Gene Deletion; D015674:Mammary Neoplasms, Animal / Q000235:genetics*; D018832:Molecular Chaperones / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics
chemical_list: D018832:Molecular Chaperones; D021122:Protein Subunits; C112806:prefoldin