dc.contributor.author
Schweizer, Leonille
dc.contributor.author
Thierfelder, Felix
dc.contributor.author
Thomas, Christian
dc.contributor.author
Soschinski, Patrick
dc.contributor.author
Kim, Hee‐Yeong
dc.contributor.author
Jödicke, Ruben
dc.contributor.author
Woltering, Niklas
dc.contributor.author
Förster, Alexandra
dc.contributor.author
Teichmann, Daniel
dc.contributor.author
Siewert, Christin
dc.contributor.author
Klein, Katharina
dc.contributor.author
Schmid, Simone
dc.contributor.author
Nunninger, Maximilian
dc.contributor.author
Thomale, Ulrich‐Wilhelm
dc.contributor.author
Onken, Julia
dc.contributor.author
Mühleisen, Helmut
dc.contributor.author
Schittenhelm, Jens
dc.contributor.author
Tatagiba, Marcos
dc.contributor.author
Deimling, Andreas von
dc.contributor.author
Reuss, David E.
dc.contributor.author
Solomon, David A.
dc.contributor.author
Heppner, Frank L.
dc.contributor.author
Koch, Arend
dc.contributor.author
Hartmann, Christian
dc.contributor.author
Staszewski, Ori
dc.contributor.author
Capper, David
dc.date.accessioned
2022-11-29T14:38:22Z
dc.date.available
2022-11-29T14:38:22Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/37098
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-36812
dc.description.abstract
Aims: Although inactivation of the von Hippel-Lindau gene (VHL) on chromosome 3p25 is considered to be the major cause of hereditary endolymphatic sac tumours (ELSTs), the genetic background of sporadic ELST is largely unknown. The aim of this study was to determine the prevalence of VHL mutations in sporadic ELSTs and compare their characteristics to VHL-disease-related tumours.
Methods: Genetic and epigenetic alterations were compared between 11 sporadic and 11 VHL-disease-related ELSTs by targeted sequencing and DNA methylation analysis.
Results: VHL mutations and small deletions detected by targeted deep sequencing were identified in 9/11 sporadic ELSTs (82%). No other cancer-related genetic pathway was altered except for TERT promoter mutations in two sporadic ELST and one VHL-disease-related ELST (15%). Loss of heterozygosity of chromosome 3 was found in 6/10 (60%) VHL-disease-related and 10/11 (91%) sporadic ELSTs resulting in biallelic VHL inactivation in 8/10 (73%) sporadic ELSTs. DNA methylation profiling did not reveal differences between sporadic and VHL-disease-related ELSTs but reliably distinguished ELST from morphological mimics of the cerebellopontine angle. VHL patients were significantly younger at disease onset compared to sporadic ELSTs (29 vs. 52 years, p < 0.0001, Fisher's exact test). VHL-disease status was not associated with an increased risk of recurrence, but the presence of clear cells was found to be associated with shorter progression-free survival (p = 0.0002, log-rank test).
Conclusion: Biallelic inactivation of VHL is the main mechanism underlying ELSTs, but unknown mechanisms beyond VHL may rarely be involved in the pathogenesis of sporadic ELSTs.
en
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
DNA methylation
en
dc.subject
endolymphatic sac tumour
en
dc.subject
TERT promoter mutation
en
dc.subject
von Hippel-Lindau disease
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Molecular characterisation of sporadic endolymphatic sac tumours and comparison to von Hippel–Lindau disease‐related tumours
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1111/nan.12741
dcterms.bibliographicCitation.journaltitle
Neuropathology and Applied Neurobiology
dcterms.bibliographicCitation.number
6
dcterms.bibliographicCitation.originalpublishername
Wiley
dcterms.bibliographicCitation.pagestart
756
dcterms.bibliographicCitation.pageend
767
dcterms.bibliographicCitation.volume
47
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
DEAL Wiley
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
34091929
dcterms.isPartOf.issn
0305-1846
dcterms.isPartOf.eissn
1365-2990