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SETD2 Is Recurrentl...
SETD2 Is Recurrently Mutated in Whole-Exome Sequenced Canine Osteosarcoma
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- Sakthikumar, Sharadha (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Broad Inst, Cambridge, MA USA
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- Elvers, Ingegerd (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Inst, Cambridge, MA USA
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- Kim, Jaegil (author)
- Broad Inst, Cambridge, MA USA
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- Arendt, Maja Louise (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Univ Copenhagen, Dept Vet Clin Sci, Frederiksberg D, Denmark
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- Thomas, Rachael (author)
- North Carolina State Univ, Comparat Med Inst, Raleigh, NC USA;North Carolina State Univ, Coll Vet Med, Raleigh, NC USA
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- Turner-Maier, Jason (author)
- Broad Inst, Cambridge, MA USA
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- Swofford, Ross (author)
- Broad Inst, Cambridge, MA USA
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- Johnson, Jeremy (author)
- Broad Inst, Cambridge, MA USA
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- Schumacher, Steven E. (author)
- Broad Inst, Cambridge, MA USA
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- Alfoldi, Jessica (author)
- Broad Inst, Cambridge, MA USA
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- Axelsson, Erik (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi
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- Couto, C. Guillermo (author)
- Ohio State Univ, Ctr Vet Med, Columbus, OH 43210 USA;Ohio State Univ, Dept Vet Clin Sci, Columbus, OH 43210 USA;Couto Vet Consultants, Hilliard, OH USA
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- Kisseberth, William C. (author)
- Ohio State Univ, Ctr Vet Med, Columbus, OH 43210 USA;Ohio State Univ, Dept Vet Clin Sci, Columbus, OH 43210 USA
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- Pettersson, Mats (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Getz, Gad (author)
- Harvard Med Sch, Boston, MA USA;Broad Inst, Cambridge, MA USA;Massachusetts Gen Hosp, Boston, MA 02114 USA
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- Meadows, Jennifer (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Modiano, Jaime F. (author)
- Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA;Univ Minnesota, Stem Cell Inst, Minneapolis, MN USA;Univ Minnesota, Inst Engn & Med, Minneapolis, MN USA;Univ Minnesota, Ctr Immunol, Minneapolis, MN USA;Coll Vet Med, Dept Vet Clin Sci, St Paul, MN USA;Coll Vet Med, Anim Canc Care & Res Program, St Paul, MN USA
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- Breen, Matthew (author)
- North Carolina State Univ, Comparat Med Inst, Raleigh, NC USA;North Carolina State Univ, Coll Vet Med, Raleigh, NC USA
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- Kierczak, Marcin, 1981- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi
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- Forsberg-Nilsson, Karin (author)
- Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden
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- Marinescu, Voichita (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi
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- Lindblad-Toh, Kerstin (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Inst, Cambridge, MA USA
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(creator_code:org_t)
- AMER ASSOC CANCER RESEARCH, 2018
- 2018
- English.
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In: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 78:13, s. 3421-3431
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Osteosarcoma is a debilitating bone cancer that affects humans, especially children and adolescents. A homologous form of osteosarcoma spontaneously occurs in dogs, and its differential incidence observed across breeds allows for the investigation of tumor mutations in the context of multiple genetic backgrounds. Using whole-exome sequencing and dogs from three susceptible breeds (22 golden retrievers, 21 Rottweilers, and 23 greyhounds), we found that osteosarcoma tumors show a high frequency of somatic copy-number alterations (SCNA), affecting key oncogenes and tumor-suppressor genes. The across-breed results are similar to what has been observed for human osteosarcoma, but the disease frequency and somatic mutation counts vary in the three breeds. For all breeds, three mutational signatures (one of which has not been previously reported) and 11 significantly mutated genes were identified. TP53 was the most frequently altered gene (83% of dogs have either mutations or SCNA in TP53), recapitulating observations in human osteosarcoma. The second most frequently mutated gene, histone methyltransferase SETD2, has known roles in multiple cancers, but has not previously been strongly implicated in osteosarcoma. This study points to the likely importance of histone modifications in osteosarcoma and highlights the strong genetic similarities between human and dog osteosarcoma, suggesting that canine osteosarcoma may serve as an excellent model for developing treatment strategies in both species. Significance: Canine osteosarcoma genomics identify SETD2 as a possible oncogenic driver of osteosarcoma, and findings establish the canine model as a useful comparative model for the corresponding human disease.
Subject headings
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Sakthikumar, Sha ...
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Elvers, Ingegerd
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Kim, Jaegil
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Arendt, Maja Lou ...
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Thomas, Rachael
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Turner-Maier, Ja ...
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show more...
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Swofford, Ross
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Johnson, Jeremy
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Schumacher, Stev ...
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Alfoldi, Jessica
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Axelsson, Erik
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Couto, C. Guille ...
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Kisseberth, Will ...
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Pettersson, Mats
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Getz, Gad
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Meadows, Jennife ...
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Modiano, Jaime F ...
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Breen, Matthew
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Kierczak, Marcin ...
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Forsberg-Nilsson ...
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Marinescu, Voich ...
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Lindblad-Toh, Ke ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Genetics
- Articles in the publication
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Cancer Research
- By the university
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Uppsala University