RT Journal
A1 Decker, Brennan
A1 Davis, Brian W.
A1 Rimbault, Maud
A1 Long, Adrienne H.
A1 Karlins, Eric
A1 Jagannathan, Vidhya
A1 Reiman, Rebecca
A1 Parker, Heidi G.
A1 Drögemüller, Cord
A1 Corneveaux, Jason J.
A1 Chapman, Erica S.
A1 Trent, Jeffery M.
A1 Leeb, Tosso
A1 Huentelman, Matthew J.
A1 Wayne, Robert K.
A1 Karyadi, Danielle M.
A1 Ostrander, Elaine A.
T1 Comparison against 186 canid whole-genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor
JF Genome Research 
JO Genome Research 
YR 2015 
FD November 01 
VO 25 
IS 11 
SP 1646 
OP 1655 
DO 10.1101/gr.190314.115 
UL http://genome.cshlp.org/content/25/11/1646.abstract 
AB 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.