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SWI/SNF Alterations in Squamous Bladder Cancers.

Fabian Achenbach1, Michael Rose1, Nadina Ortiz-Brüchle1

  • 1Institute of Pathology, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany.

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|November 24, 2020
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Summary
This summary is machine-generated.

SWI/SNF complex gene loss, particularly ARID1A, is identified in squamous-differentiated bladder cancers (sq-BLCA). This finding suggests ARID1A as a potential therapeutic target for a subset of patients, especially those with co-occurring TP53 mutations and PD-L1 expression.

Keywords:
ARID1ASWI/SNF compleximmune checkpoint inhibitorssquamous bladder cancer

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • SWI/SNF complex dysfunction is implicated in various cancers.
  • The role of SWI/SNF complex alterations in squamous-differentiated bladder cancer (sq-BLCA) is not well understood.
  • Investigating these alterations may reveal therapeutic implications.

Purpose of the Study:

  • To analyze SWI/SNF complex component expression loss and genetic alterations in sq-BLCA.
  • To explore the co-occurrence of these alterations with driver mutations and PD-L1 expression.
  • To identify potential therapeutic targets in sq-BLCA.

Main Methods:

  • Analysis of SWI/SNF gene mutations (ARID1A, SMARCA2, SMARCA4, SMARCB1/INI1, SMARCC1, SMARCC2, PBRM1) in a TCGA dataset of sq-BLCA (n=45).
  • Confirmation of ARID1A alterations using Targeted Next Generation Sequencing (NGS) and immunohistochemistry.
  • Correlation analysis with driver mutations (e.g., TP53, PIK3CA) and PD-L1 expression.

Main Results:

  • ARID1A was the most frequently altered SWI/SNF gene (15%) in sq-BLCA, associated with protein downregulation.
  • ARID1A loss was confirmed by NGS and immunohistochemistry.
  • ARID1A loss showed co-occurrence with TP53 mutations but not PIK3CA mutations.
  • A subset of sq-BLCA exhibited both ARID1A protein loss and strong PD-L1 expression.

Conclusions:

  • Expression loss of SWI/SNF subunits, notably ARID1A, occurs in sq-BLCA.
  • ARID1A is a potential therapeutic target for a subgroup of sq-BLCA patients.
  • The co-occurrence of ARID1A loss and PD-L1 expression suggests potential benefit from immune checkpoint inhibitor therapy.