Deletion of the Prefoldin Subunit 5 Gene Region on Canine Chromosome 27 is a Risk Indicator for Mammary Precancerosis
World Small Animal Veterinary Association World Congress Proceedings, 2014
B. Brenig1; S. Hennecke1; J. Beck2; E. Schütz3; K. Bornemann-Kolatzki2; S. Neumann4; P. Ströbel5; I. Nolte6; H.M. Escobar7; H.B. Urnovitz8
1Molecular Biology, Institute of Veterinary Medicine, Göttingen, Germany; 2Research Unit, Chronix Biomedical, Göttingen, Germany; 3Molecular Biology & Research Unit, Institute of Veterinary Medicine & Chronix Biomedical, Göttingen, Germany; 4Small Animal Practice, Institute of Veterinary Medicine, Göttingen, Germany; 5Department of Pathology, University Medical Center Göttingen, Göttingen, Germany; 6Clinic for Small Animals, University of Veterinary Medicine Hannover, Hannover, Germany; 7Hematology Oncology and Palliative Medicine, Clinic III, Rostock, Germany; 8CSO, Chronix Biomedical, Göttingen, Germany
Introduction
Mammary tumors (MT) are the majority of neoplastic diseases in female dogs and approximately 50% are malignant. Using massive parallel sequencing, we recently detected a deletion of the potential c-Myc repressor gene PFDN5 harboring proximal end of CFA27 in 10 of 20 malignant tumors using a digital droplet PCR (ddPCR).
Aims
Aim of this study was to confirm the PFDN5 deletion in a larger number of malignant (MMT; n = 100) and benign (BMT; n = 31) tumors.
Methods
Genomic DNA was extracted from 131 MT and the corresponding PBMCs. DdPCR was performed with primers positioned 1700bp apart from the PFDN5 gene and compared to a reference amplicon on CFA32. The copy number of PFDN5 was normalized in relation to the reference amplicon.
Results
The average copy numbers of PFDN5 was 11% lower in malignant tumors (p = 0.01), whereas the corresponding PBMC genomic DNA did not differ (p = 0.25). The best delimiter derived from ROC curve analysis was 1.99, used to confirm the presence of the deletion in 51% of the malignant, but also in 20% of the benign tumors. This difference was highly significant with an odds ratio of 4.3 (95% CI: 1.6–11.5).
Conclusion
A recurrent somatic deletion of a chromosomal region on CFA27 harboring PFDN5 is present in canine MMT. Interestingly this copy number variation was also found in tumors and hyperplasia that did not show histopathological evidence of malignancy at the time of surgery. We hypothesize that the deletion of the c-Myc repressor PFDN5 gene may serve as risk indicator for precancerosis.