SWI/SNF Alterations in Squamous Bladder Cancers

dc.contributor.authorAchenbach, Fabian
dc.contributor.authorRose, Michael
dc.contributor.authorOrtiz-Brüchle, Nadina
dc.contributor.authorSeillier, Lancelot
dc.contributor.authorKnüchel, Ruth
dc.contributor.authorWeyerer, Veronika
dc.contributor.authorHartmann, Arndt
dc.contributor.authorMorsch, Ronja
dc.contributor.authorMaurer, Angela
dc.contributor.authorEcke, Thorsten H.
dc.contributor.authorGarczyk, Stefan
dc.contributor.authorGaisa, Nadine T.
dc.date.accessioned2021-01-04
dc.date.available2023-10-09T18:28:52Z
dc.date.created2020
dc.date.issued2021-01-04
dc.description.abstractDysfunction of the SWI/SNF complex has been observed in various cancers including urothelial carcinomas. However, the clinical impact of the SWI/SNF complex in squamous-differentiated bladder cancers (sq-BLCA) remains unclear. Therefore, we aimed to analyze potential expression loss and genetic alterations of (putative) key components of the SWI/SNF complex considering the co-occurrence of genetic driver mutations and PD-L1 expression as indicators for therapeutic implications. Assessment of ARID1A, SMARCA2, SMARCA4, SMARCB1/INI1, SMARCC1, SMARCC2 and PBRM1 mutations in a TCGA data set of sq-BLCA (n = 45) revealed that ARID1A was the most frequently altered SWI/SNF gene (15%) while being associated with protein downregulation. Genetic alterations and loss of ARID1A were confirmed by Targeted Next Generation Sequencing (NGS) (3/6) and immunohistochemistry (6/116). Correlation with further mutational data and PD-L1 expression revealed co-occurrence of ARID1A loss and TP53 mutations, while positive correlations with other driver mutations such as PIK3CA were not observed. Finally, a rare number of sq-BLCA samples were characterized by both ARID1A protein loss and strong PD-L1 expression suggesting a putative benefit upon immune checkpoint inhibitor therapy. Hence, for the first time, our data revealed expression loss of SWI/SNF subunits in sq-BLCA, highlighting ARID1A as a putative target of a small subgroup of patients eligible for novel therapeutic strategies.en
dc.identifier.citationGenes 11.11 (2020). <https://www.mdpi.com/2073-4425/11/11/1368>
dc.identifier.doihttps://doi.org/10.3390/genes11111368
dc.identifier.issn2073-4425
dc.identifier.opus-id15400
dc.identifier.urihttps://open.fau.de/handle/openfau/15400
dc.identifier.urnurn:nbn:de:bvb:29-opus4-154003
dc.language.isoen
dc.publisherMDPI
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.de
dc.subjectSWI/SNF complex
dc.subjectARID1A
dc.subjectsquamous bladder cancer
dc.subjectimmune checkpoint inhibitors
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleSWI/SNF Alterations in Squamous Bladder Cancersen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.date.prevpublished2020-11-19
local.journal.issue11
local.journal.titleGenes
local.journal.volume11
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.importimport
local.subject.sammlungUniversität Erlangen-Nürnberg / Eingespielte Open Access Artikel / Eingespielte Open Access Artikel 2020
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