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  • Megquier, KatherineUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Institute of Harvard and MIT, Cambridge, Massachusetts (författare)

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

  • Artikel/kapitelEngelska2019

Förlag, utgivningsår, omfång ...

  • 2019
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-399825
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-399825URI
  • https://doi.org/10.1158/1541-7786.MCR-19-0221DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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 och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Turner-Maier, JasonBroad Institute of Harvard and MIT, Cambridge, Massachusetts (författare)
  • Swofford, RossBroad Institute of Harvard and MIT, Cambridge, Massachusetts (författare)
  • Kim, Jong-HyukDepartment 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. (författare)
  • Sarver, Aaron LAnimal 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. (författare)
  • Wang, ChaoUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)chawa410 (författare)
  • Sakthikumar, SharadhaUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Institute of Harvard and MIT, Cambridge, Massachusetts.(Swepub:uu)shasa907 (författare)
  • Johnson, JeremyBroad Institute of Harvard and MIT, Cambridge, Massachusetts. (författare)
  • Koltookian, MicheleBroad Institute of Harvard and MIT, Cambridge, Massachusetts. (författare)
  • Lewellen, MitziDepartment 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. (författare)
  • Scott, Milcah CDepartment 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. (författare)
  • Schulte, Ashley JDepartment 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. (författare)
  • Borst, LukeDepartment of Clinical Sciences, North Carolina State College of Veterinary Medicine, Raleigh, North Carolina. (författare)
  • Tonomura, NorikoBroad Institute of Harvard and MIT, Cambridge, Massachusetts; Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts. (författare)
  • Alfoldi, JessicaBroad Institute of Harvard and MIT, Cambridge, Massachusetts (författare)
  • Painter, CorrieBroad Institute of Harvard and MIT, Cambridge, Massachusetts; Count Me In, Cambridge, Massachusetts (författare)
  • Thomas, RachaelDepartment of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine; Comparative Medicine Institute, Raleigh, North Carolina (författare)
  • Karlsson, Elinor KBroad 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 (författare)
  • Breen, MatthewDepartment of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine; Comparative Medicine Institute, Raleigh, North Carolina. (författare)
  • Modiano, Jaime FUniv Minnesota, Minneapolis, MN USA (författare)
  • Elvers, IngegerdUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Institute of Harvard and MIT, Cambridge, Massachusetts(Swepub:uu)ingel569 (författare)
  • Lindblad-Toh, KerstinUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Institute of Harvard and MIT, Cambridge, Massachusetts(Swepub:uu)kerli865 (författare)
  • Uppsala universitetInstitutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Molecular Cancer Research17:12, s. 2410-24211541-77861557-3125

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