Comparison against 186 canid whole-genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor
- Brennan Decker1,2,7,
- Brian W. Davis1,7,
- Maud Rimbault1,
- Adrienne H. Long3,
- Eric Karlins1,
- Vidhya Jagannathan4,
- Rebecca Reiman5,
- Heidi G. Parker1,
- Cord Drögemüller4,
- Jason J. Corneveaux5,
- Erica S. Chapman1,
- Jeffery M. Trent5,
- Tosso Leeb4,
- Matthew J. Huentelman5,
- Robert K. Wayne6,
- Danielle M. Karyadi1 and
- Elaine A. Ostrander1
- 1Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;
- 2Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, CB1 8RN, United Kingdom;
- 3Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland 20892, USA;
- 4Institute of Genetics, University of Bern, Bern, CH-3001, Switzerland;
- 5The Translational Genomics Research Institute, Phoenix, Arizona 85004, USA;
- 6Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, California 90095, USA
- Corresponding author: eostrand{at}mail.nih.gov
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↵7 These authors contributed equally to this work.
Abstract
Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world's oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder's genome from somatic mutations that must drive clonal transmissibility. We show that CTVT has undergone continuous adaptation to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly self-antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis- and immune-related genes that may represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT's dogged perseverance in canids around the world.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.190314.115.
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Freely available online through the Genome Research Open Access option.
- Received March 19, 2015.
- Accepted July 15, 2015.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
