Ovarian Adenocarcinoma in Captive North American Jaguars (Panthera onca): Tumor Characterization and Investigation of BRCA1 Mutations
American Association of Zoo Veterinarians Conference 2015
Sarah Corner1, DVM, MS, DACVP; Maciej Parys2, DVM; Dalen Agnew1,3, DVM, PhD, DACVP; Anneke Moresco3,4, DVM, PhD; Vilma Yuzbasiyan-Gurkan2, PhD
1Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA; 2Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA; 3Reproductive Health Surveillance Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA; 4Denver Zoo, Denver, CO, USA

Abstract

High numbers of ovarian adenocarcinomas have been documented in captive jaguars, which are rare in other felids.1,4 Formalin-fixed, paraffin-embedded tissues from 55 captive, female jaguars between 1988–2014 were collected. Twenty-three jaguars (40%) had ovarian carcinoma (five with bilateral tumors), 14 had mammary carcinoma, and of these, five had both ovarian and mammary carcinoma. No association has been found between ovarian cancer and the use of exogenous progestins in zoo felids, and in these cases, only nine of 23 animals with ovarian adenocarcinoma had a history of exogenous progestin exposure.2,5 An inherited germline mutation is suspected, and candidate genes include those involved in the carcinogenesis of human ovarian and breast cancer, such as BRCA1 and BRCA2.3 These tumors most often occur in middle-aged, post-reproductive jaguars, though a homozygous germline mutation in BRCA1 could lead to embryonic lethality, impairing captive breeding. To further investigate the role of BRCA1 in tumorigenesis, jaguar genomic DNA was first extracted from whole blood. Primers were designed using the domestic cat BRCA1 genomic DNA sequence. Jaguar and domestic cat genomic DNA was amplified using PCR and Sanger sequencing. Multiple variations in the jaguar BRCA1 sequence were detected, including five nonsynonymous point mutations and one three-base-pair insertion. Any association between these sequence variations and tumor development or phenotype, as well as other candidate genes, are being investigated. Knowledge of risk factors for the development of ovarian carcinoma in jaguars will assist with the medical management and breeding recommendations of this endangered species in captivity.

Acknowledgments

The authors thank participating zoological institutions for providing tissue samples and medical histories that are critical for this ongoing study. We also appreciate the support of the AAZV and the AZA Wildlife Contraception Center in this and other reproductive disease investigations, and recognize the initial work performed by Dr. Linda Munson and those in her laboratory on this project over the last 25 years.

Literature Cited

1.  Hope K, Deem SL. Retrospective study of morbidity and mortality of captive jaguars (Panthera onca) in North America, 1982–2002. Zoo Biol. 2006;25:501–512.

2.  Kazensky CA, Munson L, Seal US. The effects of melengestrol acetate on the ovaries of captive wild felids. J Zoo Wildl Med. 1998;29(1):1–5.

3.  Meindl A, Ditsch N, Kast K, Rhiem K, Schmutzler R. Hereditary breast and ovarian cancer. Dtsch Arztebl Int. 2011;108(19):323–330.

4.  Munson L. A high prevalence of ovarian papillary cystadenocarcinomas in jaguars (Panthera onca). Vet Pathol. 1994;31:5.

5.  Munson L. Contraception in felids. Theriogenology. 2006;66(1):126–134.

 

Speaker Information
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Sarah Corner, DVM, MS, DACVP
Pathobiology and Diagnostic Investigation
College of Veterinary Medicine
Michigan State University
East Lansing, MI, USA


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