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Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study

Solitary fibrous tumors (SFT) are mesenchymal neoplasms with a favorable prognosis usually originating from the visceral pleura. Rarely, they may occur at various extrapleural sites and show malignant behavior coupled with dedifferentiation. NAB2-STAT6 fusion gene and STAT6 nuclear expression are bi...

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Autores principales: Nonaka, Haruna, Kandori, Shuya, Nitta, Satoshi, Shiga, Masanobu, Nagumo, Yoshiyuki, Kimura, Tomokazu, Kawahara, Takashi, Negoro, Hiromitsu, Hoshi, Akio, Kojima, Takahiro, Kawai, Koji, Mathis, Bryan J., Tamura, Takuro, Sato, Taka-Aki, Yamato, Mariko, Noguchi, Masayuki, Nishiyama, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727594/
https://www.ncbi.nlm.nih.gov/pubmed/35004271
http://dx.doi.org/10.3389/fonc.2021.736969
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author Nonaka, Haruna
Kandori, Shuya
Nitta, Satoshi
Shiga, Masanobu
Nagumo, Yoshiyuki
Kimura, Tomokazu
Kawahara, Takashi
Negoro, Hiromitsu
Hoshi, Akio
Kojima, Takahiro
Kawai, Koji
Mathis, Bryan J.
Tamura, Takuro
Sato, Taka-Aki
Yamato, Mariko
Noguchi, Masayuki
Nishiyama, Hiroyuki
author_facet Nonaka, Haruna
Kandori, Shuya
Nitta, Satoshi
Shiga, Masanobu
Nagumo, Yoshiyuki
Kimura, Tomokazu
Kawahara, Takashi
Negoro, Hiromitsu
Hoshi, Akio
Kojima, Takahiro
Kawai, Koji
Mathis, Bryan J.
Tamura, Takuro
Sato, Taka-Aki
Yamato, Mariko
Noguchi, Masayuki
Nishiyama, Hiroyuki
author_sort Nonaka, Haruna
collection PubMed
description Solitary fibrous tumors (SFT) are mesenchymal neoplasms with a favorable prognosis usually originating from the visceral pleura. Rarely, they may occur at various extrapleural sites and show malignant behavior coupled with dedifferentiation. NAB2-STAT6 fusion gene and STAT6 nuclear expression are biomarkers for diagnosis of SFT in addition to CD34, Bcl-2, and CD99. Furthermore, several reports have shown specific NAB2-STAT6 fusion variants and loss of STAT6 protein expression are associated with malignancy. We report a rare case of retroperitoneal SFT which rapidly progressed to death within 35 days after admission. Autopsy found a primary tumor containing both benign and malignant histologies, with multiple metastatic sites similar to the malignant, dedifferentiated tumor. STAT6 was detected in the primary differentiated tumor but not in the primary dedifferentiated tumor or lung/liver metastases. However, the NAB2-STAT6 fusion gene (NAB2ex6/STAT6ex16 variant) was detected in the primary tumor and lung/liver metastases. Intriguingly, fusion gene expression at the transcriptional level was downregulated in the dedifferentiated tumors compared to the differentiated tumor. We further performed target DNA sequencing and found gene mutations in TP53, FLT3, and AR in the dedifferentiated tumors, with TP53 mutations especially found among them. We demonstrate that downregulation of NAB2-STAT6 fusion gene at the transcriptional level is associated with malignant SFT for the first time. Moreover, the present study supports the idea that TP53 mutations promote malignancy in SFTs.
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spelling pubmed-87275942022-01-06 Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study Nonaka, Haruna Kandori, Shuya Nitta, Satoshi Shiga, Masanobu Nagumo, Yoshiyuki Kimura, Tomokazu Kawahara, Takashi Negoro, Hiromitsu Hoshi, Akio Kojima, Takahiro Kawai, Koji Mathis, Bryan J. Tamura, Takuro Sato, Taka-Aki Yamato, Mariko Noguchi, Masayuki Nishiyama, Hiroyuki Front Oncol Oncology Solitary fibrous tumors (SFT) are mesenchymal neoplasms with a favorable prognosis usually originating from the visceral pleura. Rarely, they may occur at various extrapleural sites and show malignant behavior coupled with dedifferentiation. NAB2-STAT6 fusion gene and STAT6 nuclear expression are biomarkers for diagnosis of SFT in addition to CD34, Bcl-2, and CD99. Furthermore, several reports have shown specific NAB2-STAT6 fusion variants and loss of STAT6 protein expression are associated with malignancy. We report a rare case of retroperitoneal SFT which rapidly progressed to death within 35 days after admission. Autopsy found a primary tumor containing both benign and malignant histologies, with multiple metastatic sites similar to the malignant, dedifferentiated tumor. STAT6 was detected in the primary differentiated tumor but not in the primary dedifferentiated tumor or lung/liver metastases. However, the NAB2-STAT6 fusion gene (NAB2ex6/STAT6ex16 variant) was detected in the primary tumor and lung/liver metastases. Intriguingly, fusion gene expression at the transcriptional level was downregulated in the dedifferentiated tumors compared to the differentiated tumor. We further performed target DNA sequencing and found gene mutations in TP53, FLT3, and AR in the dedifferentiated tumors, with TP53 mutations especially found among them. We demonstrate that downregulation of NAB2-STAT6 fusion gene at the transcriptional level is associated with malignant SFT for the first time. Moreover, the present study supports the idea that TP53 mutations promote malignancy in SFTs. Frontiers Media S.A. 2021-12-22 /pmc/articles/PMC8727594/ /pubmed/35004271 http://dx.doi.org/10.3389/fonc.2021.736969 Text en Copyright © 2021 Nonaka, Kandori, Nitta, Shiga, Nagumo, Kimura, Kawahara, Negoro, Hoshi, Kojima, Kawai, Mathis, Tamura, Sato, Yamato, Noguchi and Nishiyama https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Nonaka, Haruna
Kandori, Shuya
Nitta, Satoshi
Shiga, Masanobu
Nagumo, Yoshiyuki
Kimura, Tomokazu
Kawahara, Takashi
Negoro, Hiromitsu
Hoshi, Akio
Kojima, Takahiro
Kawai, Koji
Mathis, Bryan J.
Tamura, Takuro
Sato, Taka-Aki
Yamato, Mariko
Noguchi, Masayuki
Nishiyama, Hiroyuki
Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study
title Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study
title_full Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study
title_fullStr Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study
title_full_unstemmed Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study
title_short Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study
title_sort case report: molecular characterization of aggressive malignant retroperitoneal solitary fibrous tumor: a case study
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727594/
https://www.ncbi.nlm.nih.gov/pubmed/35004271
http://dx.doi.org/10.3389/fonc.2021.736969
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