Cargando…

Implementation of Copy Number Variations-Based Diagnostics in Morphologically Challenging EWSR1/FUS::NFATC2 Neoplasms of the Bone and Soft Tissue

In the last decade, new tumor entities have been described, including EWSR1/FUS::NFATC2-rearranged neoplasms of different biologic behavior. To gain further insights into the behavior of these tumors, we analyzed a spectrum of EWSR1/FUS::NFATC2-rearranged neoplasms and discuss their key diagnostic a...

Descripción completa

Detalles Bibliográficos
Autores principales: Brcic, Iva, Scheipl, Susanne, Bergovec, Marko, Leithner, Andreas, Szkandera, Joanna, Sotlar, Karl, Suda, Arnold, Smolle, Maria Anna, Kraus, Tanja, Rosenberg, Andrew Eric, Liegl-Atzwanger, Bernadette, Igrec, Jasminka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9784784/
https://www.ncbi.nlm.nih.gov/pubmed/36555836
http://dx.doi.org/10.3390/ijms232416196
_version_ 1784857893221171200
author Brcic, Iva
Scheipl, Susanne
Bergovec, Marko
Leithner, Andreas
Szkandera, Joanna
Sotlar, Karl
Suda, Arnold
Smolle, Maria Anna
Kraus, Tanja
Rosenberg, Andrew Eric
Liegl-Atzwanger, Bernadette
Igrec, Jasminka
author_facet Brcic, Iva
Scheipl, Susanne
Bergovec, Marko
Leithner, Andreas
Szkandera, Joanna
Sotlar, Karl
Suda, Arnold
Smolle, Maria Anna
Kraus, Tanja
Rosenberg, Andrew Eric
Liegl-Atzwanger, Bernadette
Igrec, Jasminka
author_sort Brcic, Iva
collection PubMed
description In the last decade, new tumor entities have been described, including EWSR1/FUS::NFATC2-rearranged neoplasms of different biologic behavior. To gain further insights into the behavior of these tumors, we analyzed a spectrum of EWSR1/FUS::NFATC2-rearranged neoplasms and discuss their key diagnostic and molecular features in relation to their prognosis. We report five patients with EWSR1/FUS::NFATC2-rearranged neoplasms, including one simple bone cyst (SBC), two complex cystic bone lesions lacking morphological characteristics of SBC, and two sarcomas. In three cases, fluorescence in situ hybridization (FISH) and in all cases copy number variation (CNV) profiling and fusion analyses were performed. All patients were male, three cystic lesions occurred in children (aged 10, 14, and 17 years), and two sarcomas in adults (69 and 39 years). Fusion analysis revealed two FUS::NFATC2 rearrangements in two cystic lesions and three EWSR1::NFATC2 rearrangements in one complex cystic lesion and two sarcomas. EWSR1 FISH revealed tumor cells with break-apart signal without amplification in one complex cystic lesion and EWSR1 amplification in both sarcomas was documented. CNV analysis showed simple karyotypes in all cystic lesions, while more complex karyotypes were found in NFATC2-rearranged sarcomas. Our study supports and expands previously reported molecular findings of EWSR1/FUS::NFATC2-rearranged neoplasms. The study highlights the importance of combining radiology and morphologic features with molecular aberrations. The use of additional molecular methods, such as CNV and FISH in the routine diagnostic workup, can be crucial in providing a correct diagnosis and avoiding overtreatment.
format Online
Article
Text
id pubmed-9784784
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-97847842022-12-24 Implementation of Copy Number Variations-Based Diagnostics in Morphologically Challenging EWSR1/FUS::NFATC2 Neoplasms of the Bone and Soft Tissue Brcic, Iva Scheipl, Susanne Bergovec, Marko Leithner, Andreas Szkandera, Joanna Sotlar, Karl Suda, Arnold Smolle, Maria Anna Kraus, Tanja Rosenberg, Andrew Eric Liegl-Atzwanger, Bernadette Igrec, Jasminka Int J Mol Sci Article In the last decade, new tumor entities have been described, including EWSR1/FUS::NFATC2-rearranged neoplasms of different biologic behavior. To gain further insights into the behavior of these tumors, we analyzed a spectrum of EWSR1/FUS::NFATC2-rearranged neoplasms and discuss their key diagnostic and molecular features in relation to their prognosis. We report five patients with EWSR1/FUS::NFATC2-rearranged neoplasms, including one simple bone cyst (SBC), two complex cystic bone lesions lacking morphological characteristics of SBC, and two sarcomas. In three cases, fluorescence in situ hybridization (FISH) and in all cases copy number variation (CNV) profiling and fusion analyses were performed. All patients were male, three cystic lesions occurred in children (aged 10, 14, and 17 years), and two sarcomas in adults (69 and 39 years). Fusion analysis revealed two FUS::NFATC2 rearrangements in two cystic lesions and three EWSR1::NFATC2 rearrangements in one complex cystic lesion and two sarcomas. EWSR1 FISH revealed tumor cells with break-apart signal without amplification in one complex cystic lesion and EWSR1 amplification in both sarcomas was documented. CNV analysis showed simple karyotypes in all cystic lesions, while more complex karyotypes were found in NFATC2-rearranged sarcomas. Our study supports and expands previously reported molecular findings of EWSR1/FUS::NFATC2-rearranged neoplasms. The study highlights the importance of combining radiology and morphologic features with molecular aberrations. The use of additional molecular methods, such as CNV and FISH in the routine diagnostic workup, can be crucial in providing a correct diagnosis and avoiding overtreatment. MDPI 2022-12-19 /pmc/articles/PMC9784784/ /pubmed/36555836 http://dx.doi.org/10.3390/ijms232416196 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brcic, Iva
Scheipl, Susanne
Bergovec, Marko
Leithner, Andreas
Szkandera, Joanna
Sotlar, Karl
Suda, Arnold
Smolle, Maria Anna
Kraus, Tanja
Rosenberg, Andrew Eric
Liegl-Atzwanger, Bernadette
Igrec, Jasminka
Implementation of Copy Number Variations-Based Diagnostics in Morphologically Challenging EWSR1/FUS::NFATC2 Neoplasms of the Bone and Soft Tissue
title Implementation of Copy Number Variations-Based Diagnostics in Morphologically Challenging EWSR1/FUS::NFATC2 Neoplasms of the Bone and Soft Tissue
title_full Implementation of Copy Number Variations-Based Diagnostics in Morphologically Challenging EWSR1/FUS::NFATC2 Neoplasms of the Bone and Soft Tissue
title_fullStr Implementation of Copy Number Variations-Based Diagnostics in Morphologically Challenging EWSR1/FUS::NFATC2 Neoplasms of the Bone and Soft Tissue
title_full_unstemmed Implementation of Copy Number Variations-Based Diagnostics in Morphologically Challenging EWSR1/FUS::NFATC2 Neoplasms of the Bone and Soft Tissue
title_short Implementation of Copy Number Variations-Based Diagnostics in Morphologically Challenging EWSR1/FUS::NFATC2 Neoplasms of the Bone and Soft Tissue
title_sort implementation of copy number variations-based diagnostics in morphologically challenging ewsr1/fus::nfatc2 neoplasms of the bone and soft tissue
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9784784/
https://www.ncbi.nlm.nih.gov/pubmed/36555836
http://dx.doi.org/10.3390/ijms232416196
work_keys_str_mv AT brciciva implementationofcopynumbervariationsbaseddiagnosticsinmorphologicallychallengingewsr1fusnfatc2neoplasmsoftheboneandsofttissue
AT scheiplsusanne implementationofcopynumbervariationsbaseddiagnosticsinmorphologicallychallengingewsr1fusnfatc2neoplasmsoftheboneandsofttissue
AT bergovecmarko implementationofcopynumbervariationsbaseddiagnosticsinmorphologicallychallengingewsr1fusnfatc2neoplasmsoftheboneandsofttissue
AT leithnerandreas implementationofcopynumbervariationsbaseddiagnosticsinmorphologicallychallengingewsr1fusnfatc2neoplasmsoftheboneandsofttissue
AT szkanderajoanna implementationofcopynumbervariationsbaseddiagnosticsinmorphologicallychallengingewsr1fusnfatc2neoplasmsoftheboneandsofttissue
AT sotlarkarl implementationofcopynumbervariationsbaseddiagnosticsinmorphologicallychallengingewsr1fusnfatc2neoplasmsoftheboneandsofttissue
AT sudaarnold implementationofcopynumbervariationsbaseddiagnosticsinmorphologicallychallengingewsr1fusnfatc2neoplasmsoftheboneandsofttissue
AT smollemariaanna implementationofcopynumbervariationsbaseddiagnosticsinmorphologicallychallengingewsr1fusnfatc2neoplasmsoftheboneandsofttissue
AT kraustanja implementationofcopynumbervariationsbaseddiagnosticsinmorphologicallychallengingewsr1fusnfatc2neoplasmsoftheboneandsofttissue
AT rosenbergandreweric implementationofcopynumbervariationsbaseddiagnosticsinmorphologicallychallengingewsr1fusnfatc2neoplasmsoftheboneandsofttissue
AT lieglatzwangerbernadette implementationofcopynumbervariationsbaseddiagnosticsinmorphologicallychallengingewsr1fusnfatc2neoplasmsoftheboneandsofttissue
AT igrecjasminka implementationofcopynumbervariationsbaseddiagnosticsinmorphologicallychallengingewsr1fusnfatc2neoplasmsoftheboneandsofttissue