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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00007346naa a2200493 4500
001oai:DiVA.org:uu-446201
003SwePub
008210622s2021 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4462012 URI
0247 a https://doi.org/10.1158/1541-7786.MCR-20-09372 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Kim, Jong Hyuku 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.4 aut
2451 0a Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs Driven by Novel Gene Fusions
264 1b American Association For Cancer Research (AACR),c 2021
338 a print2 rdacarrier
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
7001 a Megquier, Kateu Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.4 aut
7001 a Thomas, Rachaelu North Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC USA.;North Carolina State Univ, Comparat Med Inst, Raleigh, NC USA.4 aut
7001 a Sarver, Aaron L.u 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.4 aut
7001 a Song, Jung Minu Univ Minnesota, Masonic Canc Ctr, 425 E River Pkwy, Minneapolis, MN 55455 USA.4 aut
7001 a Kim, Yoon Taeu York Univ, Dept Elect Engn & Comp Sci, Toronto, ON, Canada.4 aut
7001 a Cheng, Nuojinu Univ Minnesota, Coll Sci & Engn, Sch Math, Minneapolis, MN 55455 USA.4 aut
7001 a Schulte, Ashley J.u 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.4 aut
7001 a Linden, Michael A.u 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.4 aut
7001 a Murugan, Paariu 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.4 aut
7001 a Oseth, LeAnnu Univ Minnesota, Masonic Canc Ctr, 425 E River Pkwy, Minneapolis, MN 55455 USA.4 aut
7001 a Forster, Colleen L.u Univ Minnesota, Biol Mat Procurement Network BioNet, Minneapolis, MN 55455 USA.4 aut
7001 a Elvers, Ingegerdu Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Inst MIT & Harvard, Cambridge, MA 02142 USA4 aut0 (Swepub:uu)ingel569
7001 a Swofford, Rossu Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.4 aut
7001 a Turner-Maier, Jasonu Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.4 aut
7001 a Karlsson, Elinor K.u Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Univ Massachusetts, Sch Med, Worcester, MA USA.4 aut
7001 a Breen, Matthewu North 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.4 aut
7001 a Lindblad-Toh, Kerstinu Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Inst MIT & Harvard, Cambridge, MA 02142 USA4 aut0 (Swepub:uu)kerli865
7001 a Modiano, Jaime F.u 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.4 aut
7102 a 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.b Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.4 org
7730 t Molecular Cancer Researchd : American Association For Cancer Research (AACR)g 19:5, s. 847-861q 19:5<847-861x 1541-7786x 1557-3125
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-446201
8564 8u https://doi.org/10.1158/1541-7786.MCR-20-0937

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