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Abstract TMEM-020: OVARIAN ADENOCARCINOMA IN JAGUARS ( PANTHERA ONCA ): A NATURALLY-OCCURRING MODEL OF HUMAN INHERITED OVARIAN CANCER?
Abstract
Jaguars are an endangered species and represent the only felid in the Americas from the genus Panthera. Wild jaguars continue to be threatened by habitat loss and other human impacts; therefore, maintaining a healthy breeding population in zoological institutions is critical to jaguar survival. Ovarian adenocarcinoma (OC) commonly occurs in adult jaguars housed in North American zoological institutions, and is an important cause of mortality in this population. This neoplasm is very rare in domestic cats and has not been reported in other zoo felids. Archived, formalin-fixed, paraffin embedded (FFPE) reproductive tissues from 55 female jaguars were examined. OC was confirmed histologically in 22 (40%) jaguars originating from 17 zoological institutions. Seven jaguars with OC were traced back to one breeding pair, and pedigree analysis shows an autosomal dominant pattern of inheritance. The purpose of this study is to investigate
the genetic pathogenesis of ovarian adenocarcinoma in jaguars by investigating inherited germline mutations in BRCA1, BRCA2 or other cancer genes with known involvement in human ovarian and breast cancer.
A candidate gene approach was used for investigation, as minimal wild type gene sequences are available for the jaguar, and no previous studies have been undertaken to investigate genetic mechanisms of disease in this species. By utilizing genomic information available from closely related species, a targeted library preparation and next-generation sequencing approach was used to evaluate exon sequences of multiple cancer genes (n=276) in paired OC and normal FFPE tissues from each jaguar. Probes designed in this assay captured the majority of target regions, covering 92% of total base pairs within the 1.4 Mbp target region. Average depth across FFPE samples was 114x. Multiple variants were detected in jaguar
candidate genes. One variant of interest in BRCA2 exon 11 includes a single nucleotide variant in the jaguar sequence that corresponds to position c.3732 in humans. The c.3732C>G variant gives rise to the substitution p.Ser1252Arg which is predicted to be potentially deleterious. This variant was present in all jaguar samples, but demonstrates loss of heterozygosity in the jaguar ovarian adenocarcinomas compared to paired normal tissues. This variant is in the region of exon 11 containing several amino acid (BRC) repeats essential for RAD51 binding. Maintaining genetic diversity in endangered animals, such as the jaguar, while preserving
the species in zoological institutions by captive breeding is an important aspect of their conservation. Identifying a germline mutation associated with OC in jaguars would enable the identification of mutation carriers and would allow for educated breeding decisions, better disease monitoring, and earlier intervention. Jaguars may also be a naturally-occurring animal model that parallels hereditary breast and ovarian cancer syndrome in humans.
... 1,2,11,12,23 The likelihood of reproductive disease developing naturally increases with age and nulliparity, and in some cases reproductive disease can have a heritable component. 5,9 While progestin contraceptives have been associated with increased risk of uterine disease in canids and felids, 21,22 no data are available in this regard for Hyracoidea. We report on a case series of four single-sex housed females with mild to severe hydrometra. ...
In zoos, rock hyrax (Procavia capensis) are commonly maintained in groups and population control is necessary. Here we report on hydrometra prevalence in a group of rock hyraxes. Prevalence of hydrometra in this small group (4/8) far exceeds reproductive pathology prevalence previously reported for this species under managed care. Affected females were nulliparous, but had not been contracepted; instead they were maintained as a single-sex group. The first case presented as sudden death and three additional cases were diagnosed antemortem via ultrasound. Two of these underwent ovariohysterectomy to treat the severe hydrometra. The last case was a mild hydrometra and during follow-up exam was found to have spontaneously resolved. Detailed information regarding clinical presentation, diagnostics and surgical techniques are provided.
... Although this study did find high prevalence of malignant neoplasia in jaguars, malignant ovarian neoplasia was not a salient feature. This is in contrast to findings in the North American zoo population [6,33], supporting the idea that the predisposition to malignant ovarian tumors may be associated with additional mutations introduced to a closed ex situ population. ...
As evidenced by numerous case reports from zoos, neoplasia in felids is common,
but most reports are limited to Panthera species in North America or Europe. In order to obtain a wider epidemiologic understanding of neoplasia distribution, necropsy records at seven facilities (USA, Mexico, Colombia, Peru, and Brazil) were evaluated. In contrast to others, this study population (195 cases, 16 species), included many non-Panthera felids. Overall neoplasia prevalence was 28.2% (55/195). Panthera species had a higher prevalence of neoplasia than non-Panthera species (52.5%; vs. 13.0%). Lions (66.7%), jaguars (55.0%), and tigers (31.3%) had the highest species-specific prevalence of neoplasia. Neoplasms in Panthera species were more frequently malignant than in non-Panthera (86.1% vs. 55.6%). The systems most commonly affected were the reproductive,
hematolymphoid, and respiratory. The range of management conditions and more varied genetic backgrounds support a robust taxonomic pattern and suggest that the reported propensity for neoplasia in jaguars may have a genetic basis at a taxonomic level higher than species, as lions and tigers also have high prevalence. Given the high prevalence of neoplasia and high likelihood of malignancy, routine medical exams in all nondomestic felids, but Panthera species in particular, should include thorough assessments of any clinical signs of neoplasia
A 12‐year‐old female captive jaguar (Panthera onca) developed sudden severe respiratory distress and died close to the onset of clinical signs. The animal underwent mastectomy to remove neoplasms in the mammary glands 2 years prior to death. During the post‐mortem examination, multiple nodules were found in the remaining left inguinal mammary glands. Similar lesions were found in other organs. Microscopically, neoplasms were characterised by a tubulopapillary pattern with papillary projections into the central lumen of newly formed tubules (tubulopapillary mammary carcinoma). Immunohistochemistry (IHC) for oestrogen receptor, progesterone receptor and high molecular weight cytokeratin on the mammary tissue site and a metastatic site was performed with positive results. IHC for Ki‐67 was performed in the mammary lesion with positive labelling in 50% of the cells. In captive felids, malignant neoplasms may be aggressive with limited therapeutic options. Thus, attention is needed in anticipating arising tumours to support the use of control therapies and the long‐term preservation of captive jaguars.
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