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Expanding the Use of an SS18-SSX Antibody for Molecular Assays in Synovial Sarcoma
Synovial sarcoma is an aggressive malignancy that generally affects adolescents and young adults and is characterized by high rates of recurrence and metastasis, with a 10-year survival rate of about 50%. The fusion oncoprotein SS18-SSX, the product of a pathognomonic chromosomal translocation t(X;1...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Lippincott Williams & Wilkins
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444294/ https://www.ncbi.nlm.nih.gov/pubmed/35880992 http://dx.doi.org/10.1097/PAI.0000000000001049 |
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author | Raquib, Ainiah Rushdiana Hofvander, Jakob Ta, Monica Nielsen, Torsten O. |
author_facet | Raquib, Ainiah Rushdiana Hofvander, Jakob Ta, Monica Nielsen, Torsten O. |
author_sort | Raquib, Ainiah Rushdiana |
collection | PubMed |
description | Synovial sarcoma is an aggressive malignancy that generally affects adolescents and young adults and is characterized by high rates of recurrence and metastasis, with a 10-year survival rate of about 50%. The fusion oncoprotein SS18-SSX, the product of a pathognomonic chromosomal translocation t(X;18), is the oncogenic driver of this sarcoma, disrupting differentiation through widespread epigenetic dysregulation. Experimental research into SS18-SSX biology has been limited by the lack of an antibody that specifically detects the endogenous fusion oncoprotein as opposed to its native SS18 or SSX components. Recently, a rabbit monoclonal antibody was developed and made commercially available, which specifically detects the fusion junction site epitope of SS18-SSX as found in at least 95% of synovial sarcomas. Here, we characterize a suite of molecular biology assays using this new antibody, both confirming existing and reporting on novel applications. We demonstrate its high sensitivity and specificity for synovial sarcoma diagnosis on patient samples through positive immunohistochemical staining on synovial sarcoma, tissue microarray, and full face sections. In addition, we demonstrate detection of the human SS18-SSX protein when expressed in a genetically engineered mouse model of synovial sarcoma. We also demonstrate nuclear staining of SS18-SSX in synovial sarcoma cells using immunofluorescence, and visualize the interaction between SS18-SSX and the BAF complex member BRG1 through a proximity ligation assay. Lastly, we confirm the interaction between SS18-SSX and promoter regions of target genes through chromatin immunoprecipitation. This antibody represents a breakthrough in sarcoma research and has value in multiple applications to expand the knowledge of synovial sarcoma biology. |
format | Online Article Text |
id | pubmed-9444294 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-94442942022-09-13 Expanding the Use of an SS18-SSX Antibody for Molecular Assays in Synovial Sarcoma Raquib, Ainiah Rushdiana Hofvander, Jakob Ta, Monica Nielsen, Torsten O. Appl Immunohistochem Mol Morphol Research Articles Synovial sarcoma is an aggressive malignancy that generally affects adolescents and young adults and is characterized by high rates of recurrence and metastasis, with a 10-year survival rate of about 50%. The fusion oncoprotein SS18-SSX, the product of a pathognomonic chromosomal translocation t(X;18), is the oncogenic driver of this sarcoma, disrupting differentiation through widespread epigenetic dysregulation. Experimental research into SS18-SSX biology has been limited by the lack of an antibody that specifically detects the endogenous fusion oncoprotein as opposed to its native SS18 or SSX components. Recently, a rabbit monoclonal antibody was developed and made commercially available, which specifically detects the fusion junction site epitope of SS18-SSX as found in at least 95% of synovial sarcomas. Here, we characterize a suite of molecular biology assays using this new antibody, both confirming existing and reporting on novel applications. We demonstrate its high sensitivity and specificity for synovial sarcoma diagnosis on patient samples through positive immunohistochemical staining on synovial sarcoma, tissue microarray, and full face sections. In addition, we demonstrate detection of the human SS18-SSX protein when expressed in a genetically engineered mouse model of synovial sarcoma. We also demonstrate nuclear staining of SS18-SSX in synovial sarcoma cells using immunofluorescence, and visualize the interaction between SS18-SSX and the BAF complex member BRG1 through a proximity ligation assay. Lastly, we confirm the interaction between SS18-SSX and promoter regions of target genes through chromatin immunoprecipitation. This antibody represents a breakthrough in sarcoma research and has value in multiple applications to expand the knowledge of synovial sarcoma biology. Lippincott Williams & Wilkins 2022-09 2022-07-27 /pmc/articles/PMC9444294/ /pubmed/35880992 http://dx.doi.org/10.1097/PAI.0000000000001049 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
spellingShingle | Research Articles Raquib, Ainiah Rushdiana Hofvander, Jakob Ta, Monica Nielsen, Torsten O. Expanding the Use of an SS18-SSX Antibody for Molecular Assays in Synovial Sarcoma |
title | Expanding the Use of an SS18-SSX Antibody for Molecular Assays in Synovial Sarcoma |
title_full | Expanding the Use of an SS18-SSX Antibody for Molecular Assays in Synovial Sarcoma |
title_fullStr | Expanding the Use of an SS18-SSX Antibody for Molecular Assays in Synovial Sarcoma |
title_full_unstemmed | Expanding the Use of an SS18-SSX Antibody for Molecular Assays in Synovial Sarcoma |
title_short | Expanding the Use of an SS18-SSX Antibody for Molecular Assays in Synovial Sarcoma |
title_sort | expanding the use of an ss18-ssx antibody for molecular assays in synovial sarcoma |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444294/ https://www.ncbi.nlm.nih.gov/pubmed/35880992 http://dx.doi.org/10.1097/PAI.0000000000001049 |
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