Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors

SIMPLE SUMMARY: A solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that can arise at any body location. Local or distant recurrences occur in a significant proportion of cases, but these recurrences are difficult to predict using clinical or pathological features. A specific genetic alter...

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Autores principales: Salguero-Aranda, Carmen, Martínez-Reguera, Paula, Marcilla, David, de Álava, Enrique, Díaz-Martín, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534228/
https://www.ncbi.nlm.nih.gov/pubmed/34680383
http://dx.doi.org/10.3390/cancers13205237
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author Salguero-Aranda, Carmen
Martínez-Reguera, Paula
Marcilla, David
de Álava, Enrique
Díaz-Martín, Juan
author_facet Salguero-Aranda, Carmen
Martínez-Reguera, Paula
Marcilla, David
de Álava, Enrique
Díaz-Martín, Juan
author_sort Salguero-Aranda, Carmen
collection PubMed
description SIMPLE SUMMARY: A solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that can arise at any body location. Local or distant recurrences occur in a significant proportion of cases, but these recurrences are difficult to predict using clinical or pathological features. A specific genetic alteration, the gene fusion NAB2-STAT6, is considered to be the defining driver mutation, and different fusion variants seem to account for specific clinical and pathological features, but their prognostic value remains controversial. We inspected a series of 83 SFTs with a high rate of recurrence to evaluate the clinical significance of several potential biomarkers in addition to gene fusion. Our findings confirm previous observations and uncover novel associations of molecular alterations with clinical features, adding additional evidence for their potential application as molecular biomarkers that are helpful to predict the course of the disease. ABSTRACT: Risk stratification of solitary fibrous tumor (SFT) patients based on clinicopathological features has limited efficacy, especially in predicting late relapse or metastasis. The hallmark alteration of SFT is the gene fusion NAB2-STAT6, whose prognostic value remains controversial. As biological knowledge of this entity has increased in recent years, new molecular alterations have emerged that could be helpful to refine current risk models. Here, we evaluated NAB2-STAT6 fusion variants and other molecular alterations in a series of 83 SFTs that are enriched in progressing cases. Gene fusion variants were identified by targeted RNA-seq in the whole series, whereas TERT promoter (pTERT) mutations were inspected by Sanger sequencing in a subset of 18 cases. Immunohistochemical assays were performed to assess BCOR and NTRK expression as well as P53 mutation status in 45, 44, and 44 cases, respectively. While confirming the associations of gene fusion variants with clinicopathological parameters, our results do not prove their prognostic value. Pan-TRK immunoexpresion correlated with recurrence/progression, P53 staining associated with higher mitotic counts, and pTERT mutations were enriched in cases with fatal outcome. An intriguing correlation was found for BCOR protein expression with gene fusion variants, size, and tumor location.
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spelling pubmed-85342282021-10-23 Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors Salguero-Aranda, Carmen Martínez-Reguera, Paula Marcilla, David de Álava, Enrique Díaz-Martín, Juan Cancers (Basel) Article SIMPLE SUMMARY: A solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that can arise at any body location. Local or distant recurrences occur in a significant proportion of cases, but these recurrences are difficult to predict using clinical or pathological features. A specific genetic alteration, the gene fusion NAB2-STAT6, is considered to be the defining driver mutation, and different fusion variants seem to account for specific clinical and pathological features, but their prognostic value remains controversial. We inspected a series of 83 SFTs with a high rate of recurrence to evaluate the clinical significance of several potential biomarkers in addition to gene fusion. Our findings confirm previous observations and uncover novel associations of molecular alterations with clinical features, adding additional evidence for their potential application as molecular biomarkers that are helpful to predict the course of the disease. ABSTRACT: Risk stratification of solitary fibrous tumor (SFT) patients based on clinicopathological features has limited efficacy, especially in predicting late relapse or metastasis. The hallmark alteration of SFT is the gene fusion NAB2-STAT6, whose prognostic value remains controversial. As biological knowledge of this entity has increased in recent years, new molecular alterations have emerged that could be helpful to refine current risk models. Here, we evaluated NAB2-STAT6 fusion variants and other molecular alterations in a series of 83 SFTs that are enriched in progressing cases. Gene fusion variants were identified by targeted RNA-seq in the whole series, whereas TERT promoter (pTERT) mutations were inspected by Sanger sequencing in a subset of 18 cases. Immunohistochemical assays were performed to assess BCOR and NTRK expression as well as P53 mutation status in 45, 44, and 44 cases, respectively. While confirming the associations of gene fusion variants with clinicopathological parameters, our results do not prove their prognostic value. Pan-TRK immunoexpresion correlated with recurrence/progression, P53 staining associated with higher mitotic counts, and pTERT mutations were enriched in cases with fatal outcome. An intriguing correlation was found for BCOR protein expression with gene fusion variants, size, and tumor location. MDPI 2021-10-19 /pmc/articles/PMC8534228/ /pubmed/34680383 http://dx.doi.org/10.3390/cancers13205237 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
Salguero-Aranda, Carmen
Martínez-Reguera, Paula
Marcilla, David
de Álava, Enrique
Díaz-Martín, Juan
Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors
title Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors
title_full Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors
title_fullStr Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors
title_full_unstemmed Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors
title_short Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors
title_sort evaluation of nab2-stat6 fusion variants and other molecular alterations as prognostic biomarkers in a case series of 83 solitary fibrous tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534228/
https://www.ncbi.nlm.nih.gov/pubmed/34680383
http://dx.doi.org/10.3390/cancers13205237
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