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Sökning: onr:"swepub:oai:DiVA.org:uu-268799" > Exome sequencing of...

Exome sequencing of lymphomas from three dog breeds reveals somatic mutation patterns reflecting genetic background

Elvers, Ingegerd (författare)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Broad Inst, Cambridge, MA 02142 USA.
Turner-Maier, Jason (författare)
Broad Inst, Cambridge, MA 02142 USA.
Swofford, Ross (författare)
Broad Inst, Cambridge, MA 02142 USA.
visa fler...
Koltookian, Michele (författare)
Broad Inst, Cambridge, MA 02142 USA.
Johnson, Jeremy (författare)
Broad Inst, Cambridge, MA 02142 USA.
Stewart, Chip (författare)
Broad Inst, Cambridge, MA 02142 USA.
Zhang, Cheng-Zhong (författare)
Broad Inst, Cambridge, MA 02142 USA.;Dana Farber Canc Inst, Boston, MA 02215 USA.
Schumacher, Steven E. (författare)
Broad Inst, Cambridge, MA 02142 USA.;Dana Farber Canc Inst, Boston, MA 02215 USA.
Beroukhim, Rameen (författare)
Broad Inst, Cambridge, MA 02142 USA.;Dana Farber Canc Inst, Boston, MA 02215 USA.
Rosenberg, Mara (författare)
Broad Inst, Cambridge, MA 02142 USA.
Thomas, Rachael (författare)
N Carolina State Univ, Raleigh, NC 27695 USA.
Mauceli, Evan (författare)
Broad Inst, Cambridge, MA 02142 USA.
Getz, Gad (författare)
Broad Inst, Cambridge, MA 02142 USA.;Harvard Univ, Sch Med, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.
Di Palma, Federica (författare)
Broad Inst, Cambridge, MA 02142 USA.
Modiano, Jaime F. (författare)
Univ Minnesota, Coll Vet Med, Anim Canc Care & Res Program, Minneapolis, MN 55455 USA.;Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
Breen, Matthew (författare)
N Carolina State Univ, Raleigh, NC 27695 USA.;Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA.
Lindblad-Toh, Kerstin (författare)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Broad Inst, Cambridge, MA 02142 USA.
Alfoeldi, Jessica (författare)
Broad Inst, Cambridge, MA 02142 USA.
visa färre...
 (creator_code:org_t)
2015
2015
Engelska.
Ingår i: ; 25:11, s. 1634-1645
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
NATURVETENSKAP  -- Biologiska vetenskaper -- Biokemi och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
NATURVETENSKAP  -- Biologi (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences (hsv//eng)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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