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The genomic basis of tumor regression in Tasmanian devils (Sarcophilus harrisii)


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Margres, MJ, Ruiz-Aravena, M, Hamede, R ORCID: 0000-0003-1526-225X, Jones, ME ORCID: 0000-0001-7558-9022, Lawrance, MF, Hendricks, SA, Patton, A, Davis, BW, Ostrande, EA, McCallum, H, Hohenlohe, PA and Storfer, A 2018 , 'The genomic basis of tumor regression in Tasmanian devils (Sarcophilus harrisii)' , Genome Biology and Evolution, vol. 10, no. 11 , pp. 3012-3025 , doi: 10.1093/gbe/evy229.

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Understanding the genetic basis of disease-related phenotypes, such as cancer susceptibility, is crucial for the advancement of personalized medicine. Although most cancers are somatic in origin, a small number of transmissible cancers have been documented. Two such cancers have emerged in the Tasmanian devil (Sarcophilus harrisii) and now threaten the species with extinction. Recently, cases of natural tumor regression in Tasmanian devils infected with the clonally contagious cancer have been detected. We used whole-genome sequencing and FST-based approaches to identify the genetic basis of tumor regression by comparing the genomes of seven individuals that underwent tumor regression with those of three infected individuals that did not. We found three highly differentiated candidate genomic regions containing several genes related to immune response and/or cancer risk, indicating that the genomic basis of tumor regression was polygenic. Within these genomic regions, we identified putative regulatory variation in candidate genes but no nonsynonymous variation, suggesting that natural tumor regression may be driven, at least in part, by differential host expression of key loci. Comparative oncology can provide insight into the genetic basis of cancer risk, tumor development, and the pathogenicity of cancer, particularly due to our limited ability to monitor natural, untreated tumor progression in human patients. Our results support the hypothesis that host immune response is necessary for triggering tumor regression, providing candidate genes that may translate to novel treatments in human and nonhuman cancers.

Item Type: Article
Authors/Creators:Margres, MJ and Ruiz-Aravena, M and Hamede, R and Jones, ME and Lawrance, MF and Hendricks, SA and Patton, A and Davis, BW and Ostrande, EA and McCallum, H and Hohenlohe, PA and Storfer, A
Keywords: Tasmanian devil, devil facial tumour disease, wildlife disease
Journal or Publication Title: Genome Biology and Evolution
Publisher: Oxford University Press
ISSN: 1759-6653
DOI / ID Number: 10.1093/gbe/evy229
Copyright Information:

Copyright The Author(s) 2018. Licensed under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

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