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dc.contributor.authorKoelsche, Christian
dc.contributor.authorMynarek, Martin
dc.contributor.authorSchrimpf, Daniel
dc.contributor.authorBertero, Luca
dc.contributor.authorSerrano, Jonathan
dc.contributor.authorSahm, Felix
dc.contributor.authorReuss, David E
dc.contributor.authorHou, Yanghao
dc.contributor.authorBaumhoer, Daniel
dc.contributor.authorVokuhl, Christian
dc.contributor.authorFlucke, Uta
dc.contributor.authorPetersen, Iver
dc.contributor.authorBrück, Wolfgang
dc.contributor.authorRutkowski, Stefan
dc.contributor.authorZambrano, Sandro Casavilca
dc.contributor.authorGarcia Leon, Juan Luis
dc.contributor.authorDiaz Coronado, Rosdali Yesenia
dc.contributor.authorGessler, Manfred
dc.contributor.authorTirado, Oscar M
dc.contributor.authorMora, Jaume
dc.contributor.authorAlonso, Javier 
dc.contributor.authorGarcia Del Muro, Xavier
dc.contributor.authorEsteller, Manel
dc.contributor.authorSturm, Dominik
dc.contributor.authorEcker, Jonas
dc.contributor.authorMilde, Till
dc.contributor.authorPfister, Stefan M
dc.contributor.authorKorshunov, Andrey
dc.contributor.authorSnuderl, Matija
dc.contributor.authorMechtersheimer, Gunhild
dc.contributor.authorSchüller, Ulrich
dc.contributor.authorJones, David T W
dc.contributor.authorvon Deimling, Andreas
dc.date.accessioned2020-10-27T18:51:46Z
dc.date.available2020-10-27T18:51:46Z
dc.date.issued2018
dc.identifier.citationActa Neuropathol . 2018 Aug;136(2):327-337.es_ES
dc.identifier.issn0001-6322
dc.identifier.urihttp://hdl.handle.net/20.500.12105/11225
dc.description.abstractPatients with DICER1 predisposition syndrome have an increased risk to develop pleuropulmonary blastoma, cystic nephroma, embryonal rhabdomyosarcoma, and several other rare tumor entities. In this study, we identified 22 primary intracranial sarcomas, including 18 in pediatric patients, with a distinct methylation signature detected by array-based DNA-methylation profiling. In addition, two uterine rhabdomyosarcomas sharing identical features were identified. Gene panel sequencing of the 22 intracranial sarcomas revealed the almost unifying feature of DICER1 hotspot mutations (21/22; 95%) and a high frequency of co-occurring TP53 mutations (12/22; 55%). In addition, 17/22 (77%) sarcomas exhibited alterations in the mitogen-activated protein kinase pathway, most frequently affecting the mutational hotspots of KRAS (8/22; 36%) and mutations or deletions of NF1 (7/22; 32%), followed by mutations of FGFR4 (2/22; 9%), NRAS (2/22; 9%), and amplification of EGFR (1/22; 5%). A germline DICER1 mutation was detected in two of five cases with constitutional DNA available. Notably, none of the patients showed evidence of a cancer-related syndrome at the time of diagnosis. In contrast to the genetic findings, the morphological features of these tumors were less distinctive, although rhabdomyoblasts or rhabdomyoblast-like cells could retrospectively be detected in all cases. The identified combination of genetic events indicates a relationship between the intracranial tumors analyzed and DICER1 predisposition syndrome-associated sarcomas such as embryonal rhabdomyosarcoma or the recently described group of anaplastic sarcomas of the kidney. However, the intracranial tumors in our series were initially interpreted to represent various tumor types, but rhabdomyosarcoma was not among the typical differential diagnoses considered. Given the rarity of intracranial sarcomas, this molecularly clearly defined group comprises a considerable fraction thereof. We therefore propose the designation "spindle cell sarcoma with rhabdomyosarcoma-like features, DICER1 mutant" for this intriguing group.es_ES
dc.language.isoenges_ES
dc.publisherSpringer es_ES
dc.type.hasVersionAMes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshDEAD-box RNA Helicases es_ES
dc.subject.meshDNA Methylation es_ES
dc.subject.meshFemale es_ES
dc.subject.meshGenetic Predisposition to Disease es_ES
dc.subject.meshGerm-Line Mutation es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMale es_ES
dc.subject.meshMutation es_ES
dc.subject.meshRetrospective Studies es_ES
dc.subject.meshRhabdomyosarcoma, Embryonal es_ES
dc.subject.meshRibonuclease III es_ES
dc.subject.meshSarcoma es_ES
dc.titlePrimary intracranial spindle cell sarcoma with rhabdomyosarcoma-like features share a highly distinct methylation profile and DICER1 mutations.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID29881993es_ES
dc.format.volume136es_ES
dc.format.number2es_ES
dc.format.page327-337es_ES
dc.identifier.doi10.1007/s00401-018-1871-6es_ES
dc.contributor.funderGerman Cancer Aid 
dc.contributor.funderFriedberg Charitable Foundation
dc.contributor.funderSohn Conference Foundation 
dc.contributor.funderFördergemeinschaft Kinderkrebs-Zentrum Hamburg 
dc.contributor.funderDamp Foundation 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1432-0533
dc.relation.publisherversionhttps://doi.org/10.1007/s00401-018-1871-6es_ES
dc.identifier.journalActa neuropathologicaes_ES
dc.repisalud.centroISCIII::Instituto de Investigación de Enfermedades Rarases_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES


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Atribución-NoComercial-CompartirIgual 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución-NoComercial-CompartirIgual 4.0 Internacional