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Exome sequencing of lymphomas from three dog breeds reveals somatic mutation patterns reflecting genetic background.
Elvers, Ingegerd; Turner-Maier, Jason; Swofford, Ross; Koltookian, Michele; Johnson, Jeremy; Stewart, Chip; Zhang, Cheng-Zhong; Schumacher, Steven E; Beroukhim, Rameen; Rosenberg, Mara; Thomas, Rachael; Mauceli, Evan; Getz, Gad; Palma, Federica Di; Modiano, Jaime F; Breen, Matthew; Lindblad-Toh, Kerstin; Alföldi, Jessica.
Afiliação
  • Elvers I; Broad Institute, Cambridge, Massachusetts 02142, USA; Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala SE 751 23, Sweden;
  • Turner-Maier J; Broad Institute, Cambridge, Massachusetts 02142, USA;
  • Swofford R; Broad Institute, Cambridge, Massachusetts 02142, USA;
  • Koltookian M; Broad Institute, Cambridge, Massachusetts 02142, USA;
  • Johnson J; Broad Institute, Cambridge, Massachusetts 02142, USA;
  • Stewart C; Broad Institute, Cambridge, Massachusetts 02142, USA;
  • Zhang CZ; Broad Institute, Cambridge, Massachusetts 02142, USA; Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;
  • Schumacher SE; Broad Institute, Cambridge, Massachusetts 02142, USA; Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;
  • Beroukhim R; Broad Institute, Cambridge, Massachusetts 02142, USA; Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;
  • Rosenberg M; Broad Institute, Cambridge, Massachusetts 02142, USA;
  • Thomas R; North Carolina State University, Raleigh, North Carolina 27695, USA;
  • Mauceli E; Broad Institute, Cambridge, Massachusetts 02142, USA;
  • Getz G; Broad Institute, Cambridge, Massachusetts 02142, USA; Harvard Medical School, Boston, Massachusetts 02115, USA; Massachusetts General Hospital, Boston, Massachusetts 02114, USA;
  • Palma FD; Broad Institute, Cambridge, Massachusetts 02142, USA;
  • Modiano JF; Animal Cancer Care and Research Program, College of Veterinary Medicine, and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA;
  • Breen M; North Carolina State University, Raleigh, North Carolina 27695, USA; University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina 27514, USA.
  • Lindblad-Toh K; Broad Institute, Cambridge, Massachusetts 02142, USA; Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala SE 751 23, Sweden;
  • Alföldi J; Broad Institute, Cambridge, Massachusetts 02142, USA;
Genome Res ; 25(11): 1634-45, 2015 Nov.
Article em En | MEDLINE | ID: mdl-26377837
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma de Células B / Cães / Exoma / Patrimônio Genético Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Genome Res Assunto da revista: BIOLOGIA MOLECULAR / GENETICA Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma de Células B / Cães / Exoma / Patrimônio Genético Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Genome Res Assunto da revista: BIOLOGIA MOLECULAR / GENETICA Ano de publicação: 2015 Tipo de documento: Article