dc.contributor.author
Schmiester, Maren
dc.contributor.author
Dolnik, Anna
dc.contributor.author
Kornak, Uwe
dc.contributor.author
Pfitzner, Berit
dc.contributor.author
Hummel, Michael
dc.contributor.author
Treue, Denise
dc.contributor.author
Hartmann, Arndt
dc.contributor.author
Agaimy, Abbas
dc.contributor.author
Weyerer, Veronika
dc.contributor.author
Lekaj, Anja
dc.contributor.author
Brakemeier, Susanne
dc.contributor.author
Peters, Robert
dc.contributor.author
Öllinger, Robert
dc.contributor.author
Märdian, Sven
dc.contributor.author
Bullinger, Lars
dc.contributor.author
Striefler, Jana Käthe
dc.contributor.author
Flörcken, Anne
dc.date.accessioned
2021-11-16T10:20:37Z
dc.date.available
2021-11-16T10:20:37Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/32724
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-32450
dc.description.abstract
Perivascular epithelioid cell tumors (PEComas) form a family of rare mesenchymal neoplasms that typically display myomelanocytic differentiation. Upregulation of mTOR signaling due the inactivation of TSC1/2 (Tuberous Sclerosis 1 and 2) is believed to be a key oncogenic driver in this disease. Recently, a subgroup of PEComas harboring TFE3 (Transcription Factor E3) rearrangements and presenting with a distinctive morphology has been identified. TSC1/2 and TFE3 aberrations are deemed to be mutually exclusive in PEComa, with two different pathogenic mechanisms assumed to lead to tumorigenesis. Here, we challenge this dichotomy by presenting a case of a clinically aggressive TCS1-mutated PEComa displaying a TFE3-altered phenotype. FISH analysis was suggestive of a TFE3 inversion; however, RNA and whole genome sequencing was ultimately unable to identify a fusion involving the gene. However, a copy number increase of the chromosomal region encompassing TFE3 was detected and transcriptome analysis confirmed upregulation of TFE3, which was also seen at the protein level. Therefore, we believe that the TSC1/2-mTOR pathway and TFE3 overexpression can simultaneously contribute to tumorigenesis in PEComa. Our comprehensive genetic analyses add to the understanding of the complex pathogenic mechanisms underlying PEComa and harbor insights for clinical treatment options.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
whole genome sequencing
en
dc.subject
RNA sequencing
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
TFE3 activation in a TSC1‐altered malignant PEComa: challenging the dichotomy of the underlying pathogenic mechanisms
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1002/cjp2.187
dcterms.bibliographicCitation.journaltitle
The Journal of Pathology: Clinical Research
dcterms.bibliographicCitation.number
1
dcterms.bibliographicCitation.originalpublishername
Wiley
dcterms.bibliographicCitation.pagestart
3
dcterms.bibliographicCitation.pageend
9
dcterms.bibliographicCitation.volume
7
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.funding
DEAL Wiley
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
33180365
dcterms.isPartOf.eissn
2056-4538