التفاصيل البيبلوغرافية
| العنوان: |
SWI/SNF Alterations in Squamous Bladder Cancers |
| المؤلفون: |
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 |
| المصدر: |
Genes; Volume 11; Issue 11; Pages: 1368 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2020 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
SWI/SNF complex, ARID1A, squamous bladder cancer, immune checkpoint inhibitors |
| جغرافية الموضوع: |
agris |
| الوصف: |
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. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Human Genomics and Genetic Diseases; https://dx.doi.org/10.3390/genes11111368 |
| DOI: |
10.3390/genes11111368 |
| الاتاحة: |
https://doi.org/10.3390/genes11111368 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.2D8DC82A |
| قاعدة البيانات: |
BASE |