The Tasmanian Devil Transcriptome Reveals Schwann Cell Origins of a Clonally Transmissible Cancer
Be-Deviled Cancer
Recently, a deadly transmissible cancer has emerged in Tasmanian devils, the largest existing marsupial carnivore. This disease, devil facial tumor disease (DFTD), leads to the growth of large facial tumors that frequently metastasize to internal organs. DFTD is thought to be transmitted by biting, and leads to death of affected animals within months, usually by obstructing the animals' ability to feed. Consequently, in the last 10 years Tasmanian devil numbers have dropped by about 60%. There are no genetic tests, vaccines, or treatments available for this disease, and without intervention, models predict that DFTD could cause extinction of Tasmanian devils in the wild within 50 years. Several lines of evidence suggest that DFTD is transmitted as a clonal allograft, whereby the cancer cells themselves are the agents of tumor transmission. Murchison et al. (p. 84) examined this hypothesis in detail by genotyping 25 tumor-host pairs from around Tasmania at 14 microsatellite loci and at a variable mitochondrial polymorphism. DFTD tumors were indeed found to be genetically distinct from their hosts and almost completely genetically identical to one another, supporting the idea of transmission by allograft.
Abstract
The Tasmanian devil, a marsupial carnivore, is endangered because of the emergence of a transmissible cancer known as devil facial tumor disease (DFTD). This fatal cancer is clonally derived and is an allograft transmitted between devils by biting. We performed a large-scale genetic analysis of DFTD with microsatellite genotyping, a mitochondrial genome analysis, and deep sequencing of the DFTD transcriptome and microRNAs. These studies confirm that DFTD is a monophyletic clonally transmissible tumor and suggest that the disease is of Schwann cell origin. On the basis of these results, we have generated a diagnostic marker for DFTD and identify a suite of genes relevant to DFTD pathology and transmission. We provide a genomic data set for the Tasmanian devil that is applicable to cancer diagnosis, disease evolution, and conservation biology.
Get full access to this article
View all available purchase options and get full access to this article.
Already a Subscriber?Sign In
Supplementary Material
References and Notes
1
Hawkins C. E., et al., Emerging disease and population decline of an island endemic, the Tasmanian devil Sarcophilus harrisii. Biol. Conserv. 131, 307 (2006).
2
Lachish S., Jones M., McCallum H., The impact of disease on the survival and population growth rate of the Tasmanian devil. J. Anim. Ecol. 76, 926 (2007).
3
Loh R., et al., The pathology of devil facial tumor disease (DFTD) in Tasmanian Devils (Sarcophilus harrisii). Vet. Pathol. 43, 890 (2006).
4
McCallum H., et al., Distribution and impacts of Tasmanian devil facial tumor disease. EcoHealth 4, 318 (2007).
5
Pearse A. M., Swift K., Allograft theory: Transmission of devil facial-tumour disease. Nature 439, 549 (2006).
6
Siddle H. V., et al., Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial. Proc. Natl. Acad. Sci. U.S.A. 104, 16221 (2007).
7
Cooper H. L., Mackay C. M., Banfield W. G., Chromosome studies of a contagious reticulum cell sarcoma of the Syrian hamster. J. Natl. Cancer Inst. 33, 691 (1964).
8
Murgia C., Pritchard J. K., Kim S. Y., Fassati A., Weiss R. A., Clonal origin and evolution of a transmissible cancer. Cell 126, 477 (2006).
9
Rebbeck C. A., Thomas R., Breen M., Leroi A. M., Burt A., Origins and evolution of a transmissible cancer. Evolution 63, 2340 (2009).
10
McCallum H., Tasmanian devil facial tumour disease: Lessons for conservation biology. Trends Ecol. Evol. 23, 631 (2008).
11
Canfield P. J., Cunningham A. A., J. Zoo Wildl. Med. 24, 158 (1993).
12
Griner L. A., Neoplasms in Tasmanian devils (Sarcophilus harrisii). J. Natl. Cancer Inst. 62, 589 (1979).
13
Loh R., et al., The immunohistochemical characterization of devil facial tumor disease (DFTD) in the Tasmanian Devil (Sarcophilus harrisii). Vet. Pathol. 43, 896 (2006).
14
Materials and methods are available as supporting material on Science Online.
15
Jones M. E., Paetkau D., Geffen E., Moritz C., Genetic diversity and population structure of Tasmanian devils, the largest marsupial carnivore. Mol. Ecol. 13, 2197 (2004).
16
Schickel R., Boyerinas B., Park S. M., Peter M. E., MicroRNAs: Key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene 27, 5959 (2008).
17
Ueda R., et al., Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1. Proc. Natl. Acad. Sci. U.S.A. 106, 10746 (2009).
18
Svaren J., Meijer D., The molecular machinery of myelin gene transcription in Schwann cells. Glia 56, 1541 (2008).
19
Clark H. B., Minesky J. J., Agrawal D., Agrawal H. C., Myelin basic protein and P2 protein are not immunohistochemical markers for Schwann cell neoplasms: A comparative study using antisera to S-100, P2, and myelin basic proteins. Am. J. Pathol. 121, 96 (1985).
20
Dahlin L. B., Techniques of peripheral nerve repair. Scand. J. Surg. 97, 310 (2008).
21
Gold R., Archelos J. J., Hartung H. P., Mechanisms of immune regulation in the peripheral nervous system. Brain Pathol. 9, 343 (1999).
22
D. Greco, G. H. Stabenfeldt, in Textbook of Veterinary Physiology, J. G. Cunningham, Ed. (Saunders, Philadelphia, 1997).
23
Verrier J. D., et al., Peripheral myelin protein 22 is regulated post-transcriptionally by miRNA-29a. Glia 57, 1265 (2009).
24
Gregory P. A., Bracken C. P., Bert A. G., Goodall G. J., MicroRNAs as regulators of epithelial-mesenchymal transition. Cell Cycle 7, 3112 (2008).
25
Carroll S. L., Ratner N., How does the Schwann cell lineage form tumors in NF1? Glia 56, 1590 (2008).
26
Mozos E., Méndez A., Gómez-Villamandos J. C., Martín De Las Mulas J., Pérez J., Immunohistochemical characterization of canine transmissible venereal tumor. Vet. Pathol. 33, 257 (1996).
27
Marchal T., Chabanne L., Kaplanski C., Rigal D., Magnol J. P., Immunophenotype of the canine transmissible venereal tumour. Vet. Immunol. Immunopathol. 57, 1 (1997).
Information & Authors
Information
Published In
Science
Volume 327 | Issue 5961
1 January 2010
1 January 2010
Copyright
Copyright © 2010, American Association for the Advancement of Science.
Submission history
Received: 14 August 2009
Accepted: 29 October 2009
Published in print: 1 January 2010
Acknowledgments
We thank C. Harmsen and E. Noonan (DPIPWE) and J. Smith (Fort Wayne Children’s Zoo) for assistance with sample collection. We thank K. Claudio Campos, T. Dickson, S. Peck, V. Parameswaran, J. Harris, L. Stimmler, E. Hatchwell, R. Sachidanandam, Z. Xuan, M. Rasmussen, and the students and instructors of the 2006 and 2007 Cold Spring Harbor Laboratory deep-sequencing courses. The 454 sequencing was made possible by a grant from Roche Applied Sciences. E.P.M. was supported by a Sir Keith Murdoch Fellowship from the American Australian Association and an Overseas Postdoctoral Biomedical Fellowship from the Australian National Health and Medical Council (NHMRC). A.T.P., M.B., and A.H. were supported by grants from the NHMRC. A.S. was funded by a fellowship from the Human Frontier Science Program Organization. G.J.H. was supported by grants from the National Institutes of Health. H.S.B. was funded by an Australian Research Council Linkage Grant (LP0562190). E.P.M., C.T., A.K., and G.M.W. were supported by Dr. Eric Guiler Tasmanian Devil Research Grants. Sequences generated by this study have been deposited in GEO, www.ncbi.nlm.nih.gov/geo/ accession GSE18352 (miRNA) and the Short Read Archive http://www.ncbi.nlm.nih.gov/sites/entrez?db=sra accession SRA009772 (cDNA).
Authors
Metrics & Citations
Metrics
Article Usage
Altmetrics
Citations
Export citation
Select the format you want to export the citation of this publication.
Cited by
- Contemporary and historical selection in Tasmanian devils ( Sarcophilus harrisii ) support novel, polygenic response to transmissible cancer , Proceedings of the Royal Society B: Biological Sciences, 288, 1951, (20210577), (2021).https://doi.org/10.1098/rspb.2021.0577
- NLRC5 regulates expression of MHC-I and provides a target for anti-tumor immunity in transmissible cancers, Journal of Cancer Research and Clinical Oncology, 147, 7, (1973-1991), (2021).https://doi.org/10.1007/s00432-021-03601-x
- LXR stimulates a metabolic switch and reveals cholesterol homeostasis as a statin target in Tasmanian devil facial tumor disease, Cell Reports, 34, 11, (108851), (2021).https://doi.org/10.1016/j.celrep.2021.108851
- Population Genomics of Wildlife Cancer, Population Genomics: Wildlife, (385-416), (2021).https://doi.org/10.1007/13836_2020_81
- Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells, Developmental & Comparative Immunology, 115, (103882), (2021).https://doi.org/10.1016/j.dci.2020.103882
- Applications of Population Genomics for Understanding and Mitigating Wildlife Disease, Population Genomics: Wildlife, (357-383), (2021).https://doi.org/10.1007/13836_2020_73
- The immunopeptidomes of two transmissible cancers and their host have a common, dominant peptide motif, Immunology, 163, 2, (169-184), (2021).https://doi.org/10.1111/imm.13307
- Genotype data not consistent with clonal transmission of sea turtle fibropapillomatosis or goldfish schwannoma, Wellcome Open Research, 6, (219), (2021).https://doi.org/10.12688/wellcomeopenres.17073.1
- Peptide Presentations of Marsupial MHC Class I Visualize Immune Features of Lower Mammals Paralleled with Bats, The Journal of Immunology, 207, 8, (2167-2178), (2021).https://doi.org/10.4049/jimmunol.2100350
- Profile of Jennifer Marshall Graves, Proceedings of the National Academy of Sciences, 118, 43, (e2116850118), (2021).https://doi.org/10.1073/pnas.2116850118
- See more
Loading...
View Options
Get Access
Log in to view the full text
AAAS login provides access to Science for AAAS Members, and access to other journals in the Science family to users who have purchased individual subscriptions.
- Become a AAAS Member
- Activate your AAAS ID
- Purchase Access to Other Journals in the Science Family
- Account Help
Log in via OpenAthens.
Log in via Shibboleth.
More options
Register for free to read this article
As a service to the community, this article is available for free. Login or register for free to read this article.
Buy a single issue of Science for just $15 USD.
View options
PDF format
Download this article as a PDF file
Download PDF