Swi/snf alterations in squamous bladder cancers

Achenbach F, Rose M, Ortiz-Brüchle N, Seillier L, Knüchel R, Weyerer V, Hartmann A, Morsch R, Maurer A, Ecke TH, Garczyk S, Gaisa NT (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Genes Molecular Diversity Preservation International (MDPI)

Book Volume: 11

Pages Range: 1-15

Article Number: 1368

Journal Issue: 11

DOI: 10.3390/genes11111368

Abstract

Dysfunction 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.

Authors with CRIS profile

Veronika Bahlinger Institute of Pathology Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Universitätsklinikum Aachen (UKA) DE Germany (DE) Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen DE Germany (DE) HELIOS Kliniken DE Germany (DE)

How to cite

APA:

Achenbach, F., Rose, M., Ortiz-Brüchle, N., Seillier, L., Knüchel, R., Weyerer, V.,... Gaisa, N.T. (2020). Swi/snf alterations in squamous bladder cancers. Genes, 11(11), 1-15. https://doi.org/10.3390/genes11111368

MLA:

Achenbach, Fabian, et al. "Swi/snf alterations in squamous bladder cancers." Genes 11.11 (2020): 1-15.

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