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. 2015 Jul 1;10(7):e0131280.
doi: 10.1371/journal.pone.0131280. eCollection 2015.

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

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Free PMC article

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

Silvia Hennecke et al. PLoS One. .
Free PMC article

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.

Conflict of interest statement

Competing Interests: The study was funded in part by Chronix Biomedical. Authors JB, KBK, and ES are employed by the commercial company Chronix Biomedical GmbH. There are no patents, products in development or marked products to declare. This does not alter the authors’ adherence to PLOS ONE policies and sharing data and materials.

Figures

Fig 1
Fig 1. Box plot of Ki-67 scores.
Boxplots of Ki-67 score in all malignant mammary tumors (MMT), all benign mammary tumors (BMT) (*** p<0.0001), in malignant mammary tumors with (w/) and without (w/o) the PFDN5 deletion and without the carcinoma in benign tumor (* p<0.05)

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Grant support

The study was funded by Chronix Biomedical and the Institute of Veterinary Medicine of the University of Gottingen. Study design, data collection and analysis, decision to publish and preparation of the manuscript was conducted by employees of these institutions. Authors JB, KBK, and ES are employed by the commercial company Chronix Biomedical GmbH. Chronix Biomedical provided support in the form of salaries for authors JB, KBK, and ES, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the author contributions section.
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