RT Journal
A1 Elvers, Ingegerd
A1 Turner-Maier, Jason
A1 Swofford, Ross
A1 Koltookian, Michele
A1 Johnson, Jeremy
A1 Stewart, Chip
A1 Zhang, Cheng-Zhong
A1 Schumacher, Steven E.
A1 Beroukhim, Rameen
A1 Rosenberg, Mara
A1 Thomas, Rachael
A1 Mauceli, Evan
A1 Getz, Gad
A1 Palma, Federica Di
A1 Modiano, Jaime F.
A1 Breen, Matthew
A1 Lindblad-Toh, Kerstin
A1 Alföldi, Jessica
T1 Exome sequencing of lymphomas from three dog breeds reveals somatic mutation patterns reflecting genetic background
JF Genome Research 
JO Genome Research 
YR 2015 
FD November 01 
VO 25 
IS 11 
SP 1634 
OP 1645 
DO 10.1101/gr.194449.115 
UL http://genome.cshlp.org/content/25/11/1634.abstract 
AB Lymphoma is the most common hematological malignancy in developed countries. Outcome is strongly determined by molecular subtype, reflecting a need for new and improved treatment options. Dogs spontaneously develop lymphoma, and the predisposition of certain breeds indicates genetic risk factors. Using the dog breed structure, we selected three lymphoma predisposed breeds developing primarily T-cell (boxer), primarily B-cell (cocker spaniel), and with equal distribution of B- and T-cell lymphoma (golden retriever), respectively. We investigated the somatic mutations in B- and T-cell lymphomas from these breeds by exome sequencing of tumor and normal pairs. Strong similarities were evident between B-cell lymphomas from golden retrievers and cocker spaniels, with recurrent mutations in TRAF3-MAP3K14 (28% of all cases), FBXW7 (25%), and POT1 (17%). The FBXW7 mutations recurrently occur in a specific codon; the corresponding codon is recurrently mutated in human cancer. In contrast, T-cell lymphomas from the predisposed breeds, boxers and golden retrievers, show little overlap in their mutation pattern, sharing only one of their 15 most recurrently mutated genes. Boxers, which develop aggressive T-cell lymphomas, are typically mutated in the PTEN-mTOR pathway. T-cell lymphomas in golden retrievers are often less aggressive, and their tumors typically showed mutations in genes involved in cellular metabolism. We identify genes with known involvement in human lymphoma and leukemia, genes implicated in other human cancers, as well as novel genes that could allow new therapeutic options.