Comparison against 186 canid whole genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor
- Brennan Decker1,
- Brian W Davis1,
- Maud Rimbault1,
- Adrienne H Long2,
- Eric Karlins1,
- Heidi G Parker1,
- Vidhya Jagannathan3,
- Rebecca Reiman4,
- Cord Drögemüller3,
- Jason J Corneveaux4,
- Erica S Chapman1,
- Jeffery M Trent4,
- Tosso Leeb3,
- Matthew J Huentelman4,
- Robert K Wayne5,
- Danielle M Karyadi1 and
- Elaine A Ostrander1,6
- 1 Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH;
- 2 Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, NIH;
- 3 Institute of Genetics, University of Bern;
- 4 The Translational Genomics Research Institute;
- 5 Department of Ecology and Evolutionary Biology, University of California
- ↵* Corresponding author; email: eostrand{at}mail.nih.gov
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 drivers of 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.
- Received March 19, 2015.
- Accepted July 15, 2015.
- Published by Cold Spring Harbor Laboratory Press
This manuscript is Open Access.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International license), as described at http://creativecommons.org/licenses/by-nc/4.0/.
