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Advanced adenoid cystic carcinoma (ACC) is featured by SWI/SNF chromatin remodeling complex aberrations

PURPOSE: Adenoid cystic carcinoma (ACC) is a rare neurotropic cancer with slow progression occurring in salivary glands and less frequently in other body parts. ACC is featured by hyperchromatic nuclei and various mutations in genes encoding chromatin-related machineries. The ACC treatment is mainly...

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Autores principales: Jagielska, Beata, Sarnowska, Elzbieta, Rusetska, Nataliia, Jancewicz, Iga, Durzynska, Monika, Kubala, Szymon, Chmielik, Ewa, Paul, Piotr, Rutkowski, Tomasz, Sarnowski, Tomasz J., Siedlecki, Janusz A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326013/
https://www.ncbi.nlm.nih.gov/pubmed/30382367
http://dx.doi.org/10.1007/s00432-018-2783-5
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author Jagielska, Beata
Sarnowska, Elzbieta
Rusetska, Nataliia
Jancewicz, Iga
Durzynska, Monika
Kubala, Szymon
Chmielik, Ewa
Paul, Piotr
Rutkowski, Tomasz
Sarnowski, Tomasz J.
Siedlecki, Janusz A.
author_facet Jagielska, Beata
Sarnowska, Elzbieta
Rusetska, Nataliia
Jancewicz, Iga
Durzynska, Monika
Kubala, Szymon
Chmielik, Ewa
Paul, Piotr
Rutkowski, Tomasz
Sarnowski, Tomasz J.
Siedlecki, Janusz A.
author_sort Jagielska, Beata
collection PubMed
description PURPOSE: Adenoid cystic carcinoma (ACC) is a rare neurotropic cancer with slow progression occurring in salivary glands and less frequently in other body parts. ACC is featured by hyperchromatic nuclei and various mutations in genes encoding chromatin-related machineries. The ACC treatment is mainly limited to the radical surgery and radiotherapy while the chemotherapy remains ineffective. As the knowledge about molecular basis of ACC development is limited, we investigated here the molecular features of this disease. PATIENTS AND METHODS: This study included 50 patients with ACC. Transcript profiling of available ACC samples vs normal salivary gland tissue, quantitative real-time PCR (qRT-PCR) transcript level measurements and the immunohistochemistry (IHC) for SWI/SNF chromatin remodeling complex (CRC) subunits and androgen receptor on surgery-derived paraffin-embedded samples were performed. RESULTS: Transcriptomic study followed by Gene Ontology classification indicated alteration of chromatin-related processes, including downregulated transcript levels of main SWI/SNF CRC subunits and elevated expression of BRM ATPase-coding SMARCA2 gene in ACC. Subsequent IHC indicated broad accumulation of BRM ATPase and several SWI/SNF subunits, suggesting affected control of their protein level in ACC. The IHC revealed ectopic, heterogeneous expression of androgen receptor (AR) in some ACC cells. CONCLUSIONS: Our study indicated that ACC features aberrant expression of genes controlling chromatin status and structure. We found that the balance between SWI/SNF classes is moved towards the BRM ATPase-containing complex in ACC. As BRM is known to be involved in chemoresistance in cancer cells, this observation may be the likely explanation for ACC chemoresistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00432-018-2783-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-63260132019-01-23 Advanced adenoid cystic carcinoma (ACC) is featured by SWI/SNF chromatin remodeling complex aberrations Jagielska, Beata Sarnowska, Elzbieta Rusetska, Nataliia Jancewicz, Iga Durzynska, Monika Kubala, Szymon Chmielik, Ewa Paul, Piotr Rutkowski, Tomasz Sarnowski, Tomasz J. Siedlecki, Janusz A. J Cancer Res Clin Oncol Original Article – Cancer Research PURPOSE: Adenoid cystic carcinoma (ACC) is a rare neurotropic cancer with slow progression occurring in salivary glands and less frequently in other body parts. ACC is featured by hyperchromatic nuclei and various mutations in genes encoding chromatin-related machineries. The ACC treatment is mainly limited to the radical surgery and radiotherapy while the chemotherapy remains ineffective. As the knowledge about molecular basis of ACC development is limited, we investigated here the molecular features of this disease. PATIENTS AND METHODS: This study included 50 patients with ACC. Transcript profiling of available ACC samples vs normal salivary gland tissue, quantitative real-time PCR (qRT-PCR) transcript level measurements and the immunohistochemistry (IHC) for SWI/SNF chromatin remodeling complex (CRC) subunits and androgen receptor on surgery-derived paraffin-embedded samples were performed. RESULTS: Transcriptomic study followed by Gene Ontology classification indicated alteration of chromatin-related processes, including downregulated transcript levels of main SWI/SNF CRC subunits and elevated expression of BRM ATPase-coding SMARCA2 gene in ACC. Subsequent IHC indicated broad accumulation of BRM ATPase and several SWI/SNF subunits, suggesting affected control of their protein level in ACC. The IHC revealed ectopic, heterogeneous expression of androgen receptor (AR) in some ACC cells. CONCLUSIONS: Our study indicated that ACC features aberrant expression of genes controlling chromatin status and structure. We found that the balance between SWI/SNF classes is moved towards the BRM ATPase-containing complex in ACC. As BRM is known to be involved in chemoresistance in cancer cells, this observation may be the likely explanation for ACC chemoresistance. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00432-018-2783-5) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2018-10-31 2019 /pmc/articles/PMC6326013/ /pubmed/30382367 http://dx.doi.org/10.1007/s00432-018-2783-5 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article – Cancer Research
Jagielska, Beata
Sarnowska, Elzbieta
Rusetska, Nataliia
Jancewicz, Iga
Durzynska, Monika
Kubala, Szymon
Chmielik, Ewa
Paul, Piotr
Rutkowski, Tomasz
Sarnowski, Tomasz J.
Siedlecki, Janusz A.
Advanced adenoid cystic carcinoma (ACC) is featured by SWI/SNF chromatin remodeling complex aberrations
title Advanced adenoid cystic carcinoma (ACC) is featured by SWI/SNF chromatin remodeling complex aberrations
title_full Advanced adenoid cystic carcinoma (ACC) is featured by SWI/SNF chromatin remodeling complex aberrations
title_fullStr Advanced adenoid cystic carcinoma (ACC) is featured by SWI/SNF chromatin remodeling complex aberrations
title_full_unstemmed Advanced adenoid cystic carcinoma (ACC) is featured by SWI/SNF chromatin remodeling complex aberrations
title_short Advanced adenoid cystic carcinoma (ACC) is featured by SWI/SNF chromatin remodeling complex aberrations
title_sort advanced adenoid cystic carcinoma (acc) is featured by swi/snf chromatin remodeling complex aberrations
topic Original Article – Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326013/
https://www.ncbi.nlm.nih.gov/pubmed/30382367
http://dx.doi.org/10.1007/s00432-018-2783-5
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