Comparison against 186 canid whole genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor.

Decker, Brennan; Davis, Brian W; Rimbault, Maud; Long, Adrienne H; Karlins, Eric; Parker, Heidi G; Jagannathan, Vidhya; Reiman, Rebecca; Drögemüller, Cord; Corneveaux, Jason J; Chapman, Erica S; Trent, Jeffery M; Leeb, Tosso; Huentelman, Matthew J; Wayne, Robert K; Karyadi, Danielle M; Ostrander, Elaine A (2015). Comparison against 186 canid whole genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor. Genome research, 25(11), pp. 1646-1655. Cold Spring Harbor, N.Y 10.1101/gr.190314.115

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Jagannathan, Vidya; Drögemüller, Cord and Leeb, Tosso

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health

ISSN:

1549-5469

Publisher:

Cold Spring Harbor, N.Y

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

13 Aug 2015 16:20

Last Modified:

06 Jul 2016 20:44

Publisher DOI:

10.1101/gr.190314.115

PubMed ID:

26232412

BORIS DOI:

10.7892/boris.70761

URI:

https://boris.unibe.ch/id/eprint/70761

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