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Sökning: onr:"swepub:oai:DiVA.org:uu-446201" > Genomically Complex...

  • Kim, Jong HyukUniv Minnesota, Anim Canc Care & Res Program, St Paul, MN USA.;Univ Minnesota, Coll Vet Med, Dept Vet Clin Sci, St Paul, MN USA.;Univ Minnesota, Masonic Canc Ctr, 425 E River Pkwy, Minneapolis, MN 55455 USA.;Univ Minnesota, Inst Engn Med, Minneapolis, MN 55455 USA. (författare)

Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs Driven by Novel Gene Fusions

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • American Association For Cancer Research (AACR),2021
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-446201
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-446201URI
  • https://doi.org/10.1158/1541-7786.MCR-20-0937DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

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

Anmärkningar

  • Sporadic angiosarcomas are aggressive vascular sarcomas whose rarity and genomic complexity present significant obstacles in deciphering the pathogenic significance of individual genetic alterations. Numerous fusion genes have been identified across multiple types of cancers, but their existence and significance remain unclear in sporadic angiosarcomas. In this study, we leveraged RNA-sequencing data from 13 human angiosarcomas and 76 spontaneous canine hemangiosarcomas to identify fusion genes associated with spontaneous vascular malignancies. Ten novel protein-coding fusion genes, including TEX2-PECAM1 and ATP8A2-FLT1, were identified in seven of the 13 human tumors, with two tumors showing mutations of TP53. HRAS and NRAS mutations were found in angiosarcomas without fusions or TP53 mutations. We found 15 novel protein-coding fusion genes including MYO16-PTK2, GABRA3-FLT1, and AKT3-XPNPEP1 in 11 of the 76 canine hemangiosarcomas; these fusion genes were seen exclusively in tumors of the angiogenic molecular subtype that contained recurrent mutations in TP53, PIK3CA, PIK3R1, and NRAS. In particular, fusion genes and mutations of TP53 cooccurred in tumors with higher frequency than expected by random chance, and they enriched gene signatures predicting activation of angiogenic pathways. Comparative transcriptomic analysis of human angiosarcomas and canine hemangiosarcomas identified shared molecular signatures associated with activation of PI3K/AKT/mTOR pathways. Our data suggest that genome instability induced by TP53 mutations might create a predisposition for fusion events that may contribute to tumor progression by promoting selection and/or enhancing fitness through activation of convergent angiogenic pathways in this vascular malignancy. Implications: This study shows that, while drive events of malignant vasoformative tumors of humans and dogs include diverse mutations and stochastic rearrangements that create novel fusion genes, convergent transcriptional programs govern the highly conserved morphologic organization and biological behavior of these tumors in both species.

Ämnesord och genrebeteckningar

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

  • Megquier, KateBroad Inst MIT & Harvard, Cambridge, MA 02142 USA. (författare)
  • Thomas, RachaelNorth Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC USA.;North Carolina State Univ, Comparat Med Inst, Raleigh, NC USA. (författare)
  • Sarver, Aaron L.Univ Minnesota, Anim Canc Care & Res Program, St Paul, MN USA.;Univ Minnesota, Masonic Canc Ctr, 425 E River Pkwy, Minneapolis, MN 55455 USA.;Univ Minnesota, Inst Hlth Informat, Minneapolis, MN 55455 USA. (författare)
  • Song, Jung MinUniv Minnesota, Masonic Canc Ctr, 425 E River Pkwy, Minneapolis, MN 55455 USA. (författare)
  • Kim, Yoon TaeYork Univ, Dept Elect Engn & Comp Sci, Toronto, ON, Canada. (författare)
  • Cheng, NuojinUniv Minnesota, Coll Sci & Engn, Sch Math, Minneapolis, MN 55455 USA. (författare)
  • Schulte, Ashley J.Univ Minnesota, Anim Canc Care & Res Program, St Paul, MN USA.;Univ Minnesota, Coll Vet Med, Dept Vet Clin Sci, St Paul, MN USA.;Univ Minnesota, Masonic Canc Ctr, 425 E River Pkwy, Minneapolis, MN 55455 USA. (författare)
  • Linden, Michael A.Univ Minnesota, Anim Canc Care & Res Program, St Paul, MN USA.;Univ Minnesota, Masonic Canc Ctr, 425 E River Pkwy, Minneapolis, MN 55455 USA.;Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. (författare)
  • Murugan, PaariUniv Minnesota, Anim Canc Care & Res Program, St Paul, MN USA.;Univ Minnesota, Masonic Canc Ctr, 425 E River Pkwy, Minneapolis, MN 55455 USA.;Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. (författare)
  • Oseth, LeAnnUniv Minnesota, Masonic Canc Ctr, 425 E River Pkwy, Minneapolis, MN 55455 USA. (författare)
  • Forster, Colleen L.Univ Minnesota, Biol Mat Procurement Network BioNet, Minneapolis, MN 55455 USA. (författare)
  • Elvers, IngegerdUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Inst MIT & Harvard, Cambridge, MA 02142 USA(Swepub:uu)ingel569 (författare)
  • Swofford, RossBroad Inst MIT & Harvard, Cambridge, MA 02142 USA. (författare)
  • Turner-Maier, JasonBroad Inst MIT & Harvard, Cambridge, MA 02142 USA. (författare)
  • Karlsson, Elinor K.Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Univ Massachusetts, Sch Med, Worcester, MA USA. (författare)
  • Breen, MatthewNorth Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC USA.;North Carolina State Univ, Comparat Med Inst, Raleigh, NC USA.;Univ N Carolina, Canc Genet Program, Lineberger Comprehens Canc Ctr, Raleigh, NC USA. (författare)
  • Lindblad-Toh, KerstinUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Inst MIT & Harvard, Cambridge, MA 02142 USA(Swepub:uu)kerli865 (författare)
  • Modiano, Jaime F.Univ Minnesota, Anim Canc Care & Res Program, St Paul, MN USA.;Univ Minnesota, Coll Vet Med, Dept Vet Clin Sci, St Paul, MN USA.;Univ Minnesota, Masonic Canc Ctr, 425 E River Pkwy, Minneapolis, MN 55455 USA.;Univ Minnesota, Inst Engn Med, Minneapolis, MN 55455 USA.;Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.;Univ Minnesota, Ctr Immunol, Minneapolis, MN 55455 USA.;Univ Minnesota, Stem Cell Inst, Minneapolis, MN 55455 USA. (författare)
  • Univ Minnesota, Anim Canc Care & Res Program, St Paul, MN USA.;Univ Minnesota, Coll Vet Med, Dept Vet Clin Sci, St Paul, MN USA.;Univ Minnesota, Masonic Canc Ctr, 425 E River Pkwy, Minneapolis, MN 55455 USA.;Univ Minnesota, Inst Engn Med, Minneapolis, MN 55455 USA.Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Molecular Cancer Research: American Association For Cancer Research (AACR)19:5, s. 847-8611541-77861557-3125

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