Sea turtle fibropapilloma tumors share genomic drivers and therapeutic vulnerabilities with human cancers

Abstract

Wildlife populations are under intense anthropogenic pressures, with the geographic range of many species shrinking, dramatic reductions in population numbers and undisturbed habitats, and biodiversity loss. It is postulated that we are in the midst of a sixth (Anthropocene) mass extinction event, the first to be induced by human activity. Further, threatening vulnerable species is the increased rate of emerging diseases, another consequence of anthropogenic activities. Innovative approaches are required to help maintain healthy populations until the chronic underlying causes of these issues can be addressed. Fibropapillomatosis in sea turtles is one such wildlife disease. Here, we applied precision-medicine-based approaches to profile fibropapillomatosis tumors to better understand their biology, identify novel therapeutics, and gain insights into viral and environmental triggers for fibropapillomatosis. We show that fibropapillomatosis tumors share genetic vulnerabilities with human cancer types, revealing that they are amenable to treatment with human anti-cancer therapeutics.

Mutational, transcriptional and viral shedding dynamics of the marine turtle fibropapillomatosis tumor epizootic

“…A chelonian-specific herpesvirus (chelonid herpesvirus 5, ChHV5), has been implicated in driving this disease epizootic, although Koch's postulates to confirm its causative role have yet to be definitively confirmed 7,12,[23][24][25][26] . Even so, ChHV5 infection alone is not sufficient to induce FP tumor growth.…”

“…ChHV5 is globally distributed, including being present in sea turtle populations in which fibropapillomatosis tumors have never been reported 27 . An environmental co-trigger(s) seems to be the required key to both the development of fibropapillomatosis tumors and the geographic spread of the disease, with the environmental trigger correlating with anthropogenic activity 7,26,28,29 . Much uncertainty remains about the specific environmental trigger(s) and how they interact with ChHV5 and the host immunesystem to give rise to FP tumorigenesis 7 .…”

“…Much uncertainty remains about the specific environmental trigger(s) and how they interact with ChHV5 and the host immunesystem to give rise to FP tumorigenesis 7 . It is highly likely that environmental exposures induce immunosuppression in marine turtles enabling viral load to increase to the point of crossing an oncogenic threshold, similar to a number of human virally-induced cancers 3,7,26,30 . There is a paucity of knowledge concerning the molecular signaling events underpinning fibropapillomatosis tumor initiation, development and growth, with even less known about the viral and host transcriptional and mutational landscape driving FP tumorigenesis.…”

“…Similarly, open questions remain regarding whether ChHV5 is lytic or latent in FP tumors and the occurrence of viral shedding and transmission 7,26,[31][32][33][34] . Novel environmental DNA (eDNA) approaches can help resolve the dynamics of viral shedding.…”

“…While advances in our understanding of the fibropapillomatosis tumor disease epizootic in sea turtles continue to be made 7,26,27,30,[46][47][48][49][50][51][52][53] , many questions remain unanswered in relation to this enigmatic disease. There is virtually no molecular information about the relationship (e.g.…”