Genes, Vol. 11, Pages 1368: SWI/SNF Alterations in Squamous Bladder Cancers

Genes, Vol. 11, Pages 1368: SWI/SNF Alterations in Squamous Bladder Cancers Genes doi: 10.3390/genes11111368 Authors: Fabian Achenbach Michael Rose Nadina Ortiz-Brüchle Lancelot Seillier Ruth Knüchel Veronika Weyerer Arndt Hartmann Ronja Morsch Angela Maurer Thorsten H. Ecke Stefan Garczyk Nadine T. Gaisa 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...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research