TY - JOUR

T1 - Molecular characterization of a marine turtle tumor epizootic, profiling external, internal and postsurgical regrowth tumors

AU - Yetsko, Kesey

AU - Farrell, Jessica

AU - Blackburn, Nicholas B.

AU - Whitmore, Liam

AU - Stammnitz, Maximilian R.

AU - Whilde, Jenny

AU - Eastman, Catherine

AU - Ramia, Devon Rollinson

AU - Thomas, Rachel

AU - Krstic, Aleksandar

AU - Linser, Paul

AU - Creer, Simon

AU - Carvalho, Gary

AU - Devlin, Mariana A.

AU - Nahvi, Nina

AU - Leandro, Anna Cristina

AU - deMaar, Thomas W.

AU - Burkhalter, Brooke

AU - Murchison, Elizabeth P.

AU - Schnitzler, Christine

AU - Duffy, David

PY - 2021/2/1

Y1 - 2021/2/1

N2 - 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.

AB - 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.

U2 - 10.1038/s42003-021-01656-7

DO - 10.1038/s42003-021-01656-7

M3 - Article

C2 - 33526843

VL - 4

JO - Communications Biology

JF - Communications Biology

SN - 2399-3642

IS - 1

M1 - 152

ER -