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Clinicopathological and Genomic Profiles of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma Identify Overlapping Signatures with a High Mutational Burden

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare tumors developing in chronically sun-exposed skin. Clinicopathological features are similar, but they differ in prognosis, while PDS has a more aggressive course with a higher risk for local recurrence and metastases. In curr...

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Autores principales: Ak, Melike, Kahraman, Abdullah, Arnold, Fabian M., Turko, Patrick, Levesque, Mitchell P., Zoche, Martin, Ramelyte, Egle, Dummer, Reinhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303615/
https://www.ncbi.nlm.nih.gov/pubmed/34202213
http://dx.doi.org/10.3390/genes12070974
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author Ak, Melike
Kahraman, Abdullah
Arnold, Fabian M.
Turko, Patrick
Levesque, Mitchell P.
Zoche, Martin
Ramelyte, Egle
Dummer, Reinhard
author_facet Ak, Melike
Kahraman, Abdullah
Arnold, Fabian M.
Turko, Patrick
Levesque, Mitchell P.
Zoche, Martin
Ramelyte, Egle
Dummer, Reinhard
author_sort Ak, Melike
collection PubMed
description Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare tumors developing in chronically sun-exposed skin. Clinicopathological features are similar, but they differ in prognosis, while PDS has a more aggressive course with a higher risk for local recurrence and metastases. In current clinical practice, they are diagnosed by exclusion using immunohistochemistry. Thus, stringent diagnostic criteria and correct differentiation are critical in management and treatment for optimal outcomes. This retrospective single-center study collected clinicopathological data and tumor samples of 10 AFX and 18 PDS. Extracted genomic DNA from tumor specimens was analyzed by a next-generation sequencing (NGS) platform (FoundationOne-CDx™). Among 65 identified mutations, TP53 inactivating mutations were observed in all tumor specimens. In both AFX and PDS, the known pathogenic gene alterations in CDKN2A, TERT promoter, and NOTCH1 were frequently present, along with high mutational burden and stable Micro-Satellite Instability status. The mutational profiles differed only in ASXL1, which was only present in AFX. Further differences were identified in likely pathogenic and unknown gene alterations. Similarities in their genomic signatures could help to distinguish them from other malignancies, but they are not distinguishable between each other using the FoundationOne-CDx™ NGS panel. Therefore, histological criteria to determine diagnosis remain valid. For further insight, performing deep tumor profiling may be necessary.
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spelling pubmed-83036152021-07-25 Clinicopathological and Genomic Profiles of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma Identify Overlapping Signatures with a High Mutational Burden Ak, Melike Kahraman, Abdullah Arnold, Fabian M. Turko, Patrick Levesque, Mitchell P. Zoche, Martin Ramelyte, Egle Dummer, Reinhard Genes (Basel) Article Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare tumors developing in chronically sun-exposed skin. Clinicopathological features are similar, but they differ in prognosis, while PDS has a more aggressive course with a higher risk for local recurrence and metastases. In current clinical practice, they are diagnosed by exclusion using immunohistochemistry. Thus, stringent diagnostic criteria and correct differentiation are critical in management and treatment for optimal outcomes. This retrospective single-center study collected clinicopathological data and tumor samples of 10 AFX and 18 PDS. Extracted genomic DNA from tumor specimens was analyzed by a next-generation sequencing (NGS) platform (FoundationOne-CDx™). Among 65 identified mutations, TP53 inactivating mutations were observed in all tumor specimens. In both AFX and PDS, the known pathogenic gene alterations in CDKN2A, TERT promoter, and NOTCH1 were frequently present, along with high mutational burden and stable Micro-Satellite Instability status. The mutational profiles differed only in ASXL1, which was only present in AFX. Further differences were identified in likely pathogenic and unknown gene alterations. Similarities in their genomic signatures could help to distinguish them from other malignancies, but they are not distinguishable between each other using the FoundationOne-CDx™ NGS panel. Therefore, histological criteria to determine diagnosis remain valid. For further insight, performing deep tumor profiling may be necessary. MDPI 2021-06-25 /pmc/articles/PMC8303615/ /pubmed/34202213 http://dx.doi.org/10.3390/genes12070974 Text en © 2021 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
Ak, Melike
Kahraman, Abdullah
Arnold, Fabian M.
Turko, Patrick
Levesque, Mitchell P.
Zoche, Martin
Ramelyte, Egle
Dummer, Reinhard
Clinicopathological and Genomic Profiles of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma Identify Overlapping Signatures with a High Mutational Burden
title Clinicopathological and Genomic Profiles of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma Identify Overlapping Signatures with a High Mutational Burden
title_full Clinicopathological and Genomic Profiles of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma Identify Overlapping Signatures with a High Mutational Burden
title_fullStr Clinicopathological and Genomic Profiles of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma Identify Overlapping Signatures with a High Mutational Burden
title_full_unstemmed Clinicopathological and Genomic Profiles of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma Identify Overlapping Signatures with a High Mutational Burden
title_short Clinicopathological and Genomic Profiles of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma Identify Overlapping Signatures with a High Mutational Burden
title_sort clinicopathological and genomic profiles of atypical fibroxanthoma and pleomorphic dermal sarcoma identify overlapping signatures with a high mutational burden
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303615/
https://www.ncbi.nlm.nih.gov/pubmed/34202213
http://dx.doi.org/10.3390/genes12070974
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