TY  - JOUR
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
Y1  - 2015/11/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1634 
EP  - 1645 
DO  - 10.1101/gr.194449.115 
VL  - 25 
IS  - 11 
UR  - http://genome.cshlp.org/content/25/11/1634.abstract 
N2  - 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. 
ER  -