Sea turtle populations are under threat from an epizootic tumor disease (animal epidemic) known as fibropapillomatosis. Fibropapillomatosis continues to spread geographically, with prevalence of the disease also growing at many longer-affected sites globally. However, we do not yet understand the precise environmental, mutational and viral events driving fibropapillomatosis tumor formation and progression.Here we perform transcriptomic and immunohistochemical profiling of five fibropapillomatosis tumor types: external new, established and postsurgical regrowth tumors, and internal lung and kidney tumors. We reveal that internal tumors are molecularly distinct from the more common external tumors. However, they have a small number of conserved potentially therapeutically targetable molecular vulnerabilities in common, such as the MAPK, Wnt, TGFβ and TNF oncogenic signaling pathways. These conserved oncogenic drivers recapitulate remarkably well the core pan-cancer drivers responsible for human cancers. Fibropapillomatosis has been considered benign, but metastatic-related transcriptional signatures are strongly activated in kidney and established external tumors. Tumors in turtles with poor outcomes (died/euthanized) have genes associated with apoptosis and immune function suppressed, with these genes providing putative predictive biomarkers.Together, these results offer an improved understanding of fibropapillomatosis tumorigenesis and provide insights into the origins, inter-tumor relationships, and therapeutic treatment for this wildlife epizootic.
Sea turtle fibropapillomatosis (FP) is a tumor promoting disease that is one of several threats globally to endangered sea turtle populations. The prevalence of FP is highest in green sea turtle (Chelonia mydas) populations, and historically has shown considerable temporal growth. FP tumors can significantly affect the ability of turtles to forage for food and avoid predation and can grow to debilitating sizes. In the current study, based in South Texas, we have applied transcriptome sequencing to FP tumors and healthy control tissue to study the gene expression profiles of FP. By identifying differentially expressed turtle genes in FP, and matching these genes to their closest human ortholog we draw on the wealth of human based knowledge, specifically human cancer, to identify new insights into the biology of sea turtle FP. We show that several genes aberrantly expressed in FP tumors have known tumor promoting biology in humans, including CTHRC1 and NLRC5, and provide support that disruption of the Wnt signaling pathway is a feature of FP. Further, we profiled the expression of current targets of immune checkpoint inhibitors from human oncology in FP tumors and identified potential candidates for future studies.
Nine green sea turtles, Chelonia mydas, were presented to two rehabilitation facilities on the Texas coast with cutaneous growths consistent with fibropapillomatosis. Complete blood counts, radiographs, and computed tomography were performed for further evaluation. No evidence of internal tumors was present using either imaging modality. Treatment included surgical excision of the cutaneous tumors. Histopathologic analysis and polymerase chain reaction (PCR) were performed with the tissue samples collected. Histopathology revealed characteristic inclusions in only three (33%) individuals, and PCR results for fibropapilloma-associated turtle herpesvirus were positive for eight (89%) of nine individuals submitted. To our knowledge, this is the first report of fibropapillomatosis in a green sea turtle on the Texas coast.
A male thick-billed parrot (Rhynchopsitta pachyrhyncha) was diagnosed with a malignant melanoma of the mandibular beak (gnathotheca). Surgical excision was impossible because of the location of the lesion; a combination of radiation therapy and oral antitumor drugs were used to treat the neoplasm. A whole-body computed tomographic scan showed evidence of metastasis in the lungs; the bird, therefore, was considered to have stage IV disease. Throughout the treatment period, the bird showed no clinical evidence of systemic disease. The bird was given 20 treatments of localized radiation therapy of 2.5 Gray (Gy) for a cumulative dose of 50 Gy. The bird was also treated with piroxicam and cimetidine orally from the time of diagnosis, throughout radiation therapy, and until its death. By the completion of radiation therapy, the initial lesion had decreased considerably in size. The bird survived 2.5 months after radiation therapy was completed but died of complications related to metastatic disease. Necropsy results revealed metastases throughout the body, including lesions in the lungs and liver. To our knowledge, this is the first report of localized radiation therapy and oral antitumor drugs being used to treat malignant melanoma in an avian patient. The radiation therapy did produce tumor response in the form of a reduction in size of the visible tumor.
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