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Molecular characterization of a marine turtle tumor epizootic, profiling external, internal and postsurgical regrowth tumors

Published version
Peer-reviewed

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Authors

Yetsko, Kelsey 
Farrell, Jessica A.  ORCID logo  https://orcid.org/0000-0003-2303-7204
Blackburn, Nicholas B.  ORCID logo  https://orcid.org/0000-0002-9774-1539
Whitmore, Liam 
Stammnitz, Maximilian R.  ORCID logo  https://orcid.org/0000-0002-1704-9199

Abstract

Abstract: 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.

Description

Keywords

Article, /631/67, /631/158, /631/67/69, /631/67/70, /631/158/672, /38/1, /38/39, /38/91, /45, /96/95, article

Journal Title

Communications Biology

Conference Name

Journal ISSN

2399-3642

Volume Title

4

Publisher

Nature Publishing Group UK
Sponsorship
University of Cambridge (Gates Cambridge PhD scholarship)
Sea Turtle Conservancy (STC) (17-033R)
Save Our Seas Foundation (SOSF) (SOSF 356)
EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) (663830-BU115)
Irish Research Council for Science, Engineering and Technology (IRCSET) (GOIPG/2020/1056)