SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Guren Tormod K.)
 

Sökning: WFRF:(Guren Tormod K.) > Transcriptomic subt...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005538naa a2200517 4500
001oai:lup.lub.lu.se:5056eb72-33dd-4481-909f-fcc2d5517817
003SwePub
008231205s2023 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/5056eb72-33dd-4481-909f-fcc2d55178172 URI
0247 a https://doi.org/10.1016/j.ebiom.2023.1048292 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Høland, Marenu University of Oslo,Oslo university hospital4 aut
2451 0a Transcriptomic subtyping of malignant peripheral nerve sheath tumours highlights immune signatures, genomic profiles, patient survival and therapeutic targets
264 1c 2023
520 a Background: Malignant peripheral nerve sheath tumour (MPNST) is an aggressive orphan disease commonly affecting adolescents or young adults. Current knowledge of molecular tumour biology has been insufficient for development of rational treatment strategies. We aimed to discover molecular subtypes of potential clinical relevance. Methods: Fresh frozen samples of MPNSTs (n = 94) and benign neurofibromas (n = 28) from 115 patients in a European multicentre study were analysed by DNA copy number and/or transcriptomic profiling. Unsupervised transcriptomic subtyping was performed and the subtypes characterized for genomic aberrations, clinicopathological associations and patient survival. Findings: MPNSTs were classified into two transcriptomic subtypes defined primarily by immune signatures and proliferative processes. “Immune active” MPNSTs (44%) had sustained immune signals relative to neurofibromas, were more frequently low-grade (P = 0.01) and had favourable prognostic associations in a multivariable model of disease-specific survival with clinicopathological factors (hazard ratio 0.25, P = 0.003). “Immune deficient” MPNSTs were more aggressive and characterized by proliferative signatures, high genomic complexity, aberrant TP53 and PRC2 loss, as well as high relative expression of several potential actionable targets (EGFR, ERBB2, EZH2, KIF11, PLK1, RRM2). Integrated gene-wise analyses suggested a DNA copy number-basis for proliferative transcriptomic signatures in particular, and the tumour copy number burden further stratified the transcriptomic subtypes according to patient prognosis (P < 0.01). Interpretation: Approximately half of MPNSTs belong to an “immune deficient” transcriptomic subtype associated with an aggressive disease course, PRC2 loss and expression of several potential therapeutic targets, providing a rationale for molecularly-guided intervention trials. Funding: Research grants from non-profit organizations, as stated in the Acknowledgements.
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
653 a Data integration
653 a DNA copy number aberrations
653 a MPNST
653 a Prognosis
653 a Transcriptomic subtypes
7001 a Berg, Kaja C.G.u Oslo university hospital4 aut
7001 a Eilertsen, Ina A.u Oslo university hospital4 aut
7001 a Bjerkehagen, Bodilu University of Oslo,Oslo university hospital4 aut
7001 a Kolberg, Matthiasu Oslo university hospital4 aut
7001 a Boye, Kjetilu Oslo university hospital4 aut
7001 a Lingjærde, Ole Christianu University of Oslo4 aut
7001 a Guren, Tormod K.u Oslo university hospital4 aut
7001 a Mandahl, Nilsu Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Genetiska avvikelser i mjukdelstumörer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,The genetics of soft tissue tumors,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments4 aut0 (Swepub:lu)kgen-nma
7001 a van den Berg, Evau University Medical Center Groningen4 aut
7001 a Palmerini, Emanuelau Rizzoli Orthopedic Institute4 aut
7001 a Smeland, Sigbjørnu University of Oslo,Oslo university hospital4 aut
7001 a Picci, Pierou Rizzoli Orthopedic Institute4 aut
7001 a Mertens, Fredriku Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Genetiska avvikelser i mjukdelstumörer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,The genetics of soft tissue tumors,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments4 aut0 (Swepub:lu)kgen-fme
7001 a Sveen, Anitau University of Oslo,Oslo university hospital4 aut
7001 a Lothe, Ragnhild A.u Oslo university hospital,University of Oslo4 aut
7102 a University of Oslob Oslo university hospital4 org
7730 t EBioMedicineg 97q 97x 2352-3964
8564 u http://dx.doi.org/10.1016/j.ebiom.2023.104829x freey FULLTEXT
8564 8u https://lup.lub.lu.se/record/5056eb72-33dd-4481-909f-fcc2d5517817
8564 8u https://doi.org/10.1016/j.ebiom.2023.104829

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy