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

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posted on 2023-05-21, 00:46 authored by Yetsko, K, Farrell, JA, Nicholas BlackburnNicholas Blackburn, Whitmore, L, Stammnitz, MR, Whilde, J, Eastman, CB, Ramia, DR, Thomas, R, Krstic, A, Linser, P, Creer, S, Carvalho, G, Devlin, MA, Nahvi, N, Leandro, AC, deMaar, TW, Burkhalter, B, Murchison, EP, Schnitzler, C, Duffy, DJ

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.

History

Publication title

Communications Biology

Volume

4

Article number

151

Number

151

Pagination

1-16

ISSN

2399-3642

Department/School

Menzies Institute for Medical Research

Publisher

Nature Publishing Group

Place of publication

United Kingdom

Rights statement

© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons Attribution 4.0 International (CC BY 4.0) licence, (https://creativecommons.org/licenses/by/4.0/) and indicate if changes were made

Repository Status

  • Open

Socio-economic Objectives

Control of pests, diseases and exotic species in marine environments; Marine biodiversity

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