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Comparative Genomics Reveals Shared Mutational Landscape in Canine Hemangiosarcoma and Human Angiosarcoma

Megquier, Katherine (författare)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Institute of Harvard and MIT, Cambridge, Massachusetts
Turner-Maier, Jason (författare)
Broad Institute of Harvard and MIT, Cambridge, Massachusetts
Swofford, Ross (författare)
Broad Institute of Harvard and MIT, Cambridge, Massachusetts
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Kim, Jong-Hyuk (författare)
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota; Animal Cancer Care and Research Program, University of Minnesota, St. Paul, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Sarver, Aaron L (författare)
Animal Cancer Care and Research Program, University of Minnesota, St. Paul, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota; Institute for Health Informatics, University of Minnesota, Minneapolis, Minnesota.
Wang, Chao (författare)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
Sakthikumar, Sharadha (författare)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
Johnson, Jeremy (författare)
Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
Koltookian, Michele (författare)
Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
Lewellen, Mitzi (författare)
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota; Animal Cancer Care and Research Program, University of Minnesota, St. Paul, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Scott, Milcah C (författare)
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota; Animal Cancer Care and Research Program, University of Minnesota, St. Paul, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Schulte, Ashley J (författare)
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota; Animal Cancer Care and Research Program, University of Minnesota, St. Paul, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Borst, Luke (författare)
Department of Clinical Sciences, North Carolina State College of Veterinary Medicine, Raleigh, North Carolina.
Tonomura, Noriko (författare)
Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts.
Alfoldi, Jessica (författare)
Broad Institute of Harvard and MIT, Cambridge, Massachusetts
Painter, Corrie (författare)
Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Count Me In, Cambridge, Massachusetts
Thomas, Rachael (författare)
Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine; Comparative Medicine Institute, Raleigh, North Carolina
Karlsson, Elinor K (författare)
Broad Institute of Harvard and MIT, Cambridge, Massachusetts; Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
Breen, Matthew (författare)
Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine; Comparative Medicine Institute, Raleigh, North Carolina.
Modiano, Jaime F (författare)
Univ Minnesota, Minneapolis, MN USA
Elvers, Ingegerd (författare)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Institute of Harvard and MIT, Cambridge, Massachusetts
Lindblad-Toh, Kerstin (författare)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Institute of Harvard and MIT, Cambridge, Massachusetts
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 (creator_code:org_t)
2019
2019
Engelska.
Ingår i: ; 17:12, s. 2410-2421
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Angiosarcoma is a highly aggressive cancer of blood vessel-forming cells with few effective treatment options and high patient mortality. It is both rare and heterogenous, making large, well-powered genomic studies nearly impossible. Dogs commonly suffer from a similar cancer, called hemangiosarcoma, with breeds like the golden retriever carrying heritable genetic factors that put them at high risk. If the clinical similarity of canine hemangiosarcoma and human angiosarcoma reflects shared genomic etiology, dogs could be a critically needed model for advancing angiosarcoma research. We assessed the genomic landscape of canine hemangiosarcoma via whole-exome sequencing (47 golden retriever hemangiosarcomas) and RNA sequencing (74 hemangiosarcomas from multiple breeds). Somatic coding mutations occurred most frequently in the tumor suppressor TP53 (59.6% of cases) as well as two genes in the PI3K pathway: the oncogene PIK3CA (29.8%) and its regulatory subunit PIK3R1 (8.5%). The predominant mutational signature was the age-associated deamination of cytosine to thymine. As reported in human angiosarcoma, CDKN2A/B was recurrently deleted and VEGFA, KDR, and KIT recurrently gained. We compared the canine data to human data recently released by The Angiosarcoma Project, and found many of the same genes and pathways significantly enriched for somatic mutations, particularly in breast and visceral angiosarcomas. Canine hemangiosarcoma closely models the genomic landscape of human angiosarcoma of the breast and viscera, and is a powerful tool for investigating the pathogenesis of this devastating disease. IMPLICATIONS: We characterize the genomic landscape of canine hemangiosarcoma and demonstrate its similarity to human angiosarcoma.

Ämnesord

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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