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Molecular Profiling of Atypical Tenosynovial Giant Cell Tumors Reveals Novel Non-CSF1 Fusions

Tenosynovial giant cell tumor (TGCT) is a benign neoplasm characterized by recurrent fusions involving the colony-stimulating factor 1 (CSF1) gene and translocation partners including collagen type VI alpha 3 chain (COL6A3) or S100 calcium-binding protein A10 (S100A10). Herein, we report three atypi...

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Autores principales: Vougiouklakis, Theodore, Shen, Guomiao, Feng, Xiaojun, Hoda, Syed T., Jour, George
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016751/
https://www.ncbi.nlm.nih.gov/pubmed/31906059
http://dx.doi.org/10.3390/cancers12010100
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author Vougiouklakis, Theodore
Shen, Guomiao
Feng, Xiaojun
Hoda, Syed T.
Jour, George
author_facet Vougiouklakis, Theodore
Shen, Guomiao
Feng, Xiaojun
Hoda, Syed T.
Jour, George
author_sort Vougiouklakis, Theodore
collection PubMed
description Tenosynovial giant cell tumor (TGCT) is a benign neoplasm characterized by recurrent fusions involving the colony-stimulating factor 1 (CSF1) gene and translocation partners including collagen type VI alpha 3 chain (COL6A3) or S100 calcium-binding protein A10 (S100A10). Herein, we report three atypical TGCT cases with very unusual morphology comprising areas with increased cellular atypia, mitotic activity, and worrisome features that harbor unique non-CSF1 gene fusions. Anchored multiplex PCR (AMP) for next-generation sequencing utilizing a customized panel targeting 86 cancer-related genes was performed, and it identified novel non-CSF1-driven gene fusions: NIPBL-ERG, FN1-ROS1, and YAP1-MAML2. Screening of three control TGCTs with conventional morphology found translocations involving CSF1, with partner genes COL6A3, FN1, and newly identified KCNMA1. All novel fusions were further validated by reverse transcriptase-PCR (RT-PCR) and Sanger sequencing. Late and multiple local recurrences occurred in the atypical TGCTs, while no recurrences were reported in the conventional TGCTs. Our findings reveal that atypical TGCTs harbor gene fusions not implicating CSF1 and suggest that non-CSF1 fusions potentially confer greater propensity to recurrences and local aggressiveness while indicating the presence of alternate pathogenic mechanisms that warrant further investigation.
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spelling pubmed-70167512020-02-28 Molecular Profiling of Atypical Tenosynovial Giant Cell Tumors Reveals Novel Non-CSF1 Fusions Vougiouklakis, Theodore Shen, Guomiao Feng, Xiaojun Hoda, Syed T. Jour, George Cancers (Basel) Article Tenosynovial giant cell tumor (TGCT) is a benign neoplasm characterized by recurrent fusions involving the colony-stimulating factor 1 (CSF1) gene and translocation partners including collagen type VI alpha 3 chain (COL6A3) or S100 calcium-binding protein A10 (S100A10). Herein, we report three atypical TGCT cases with very unusual morphology comprising areas with increased cellular atypia, mitotic activity, and worrisome features that harbor unique non-CSF1 gene fusions. Anchored multiplex PCR (AMP) for next-generation sequencing utilizing a customized panel targeting 86 cancer-related genes was performed, and it identified novel non-CSF1-driven gene fusions: NIPBL-ERG, FN1-ROS1, and YAP1-MAML2. Screening of three control TGCTs with conventional morphology found translocations involving CSF1, with partner genes COL6A3, FN1, and newly identified KCNMA1. All novel fusions were further validated by reverse transcriptase-PCR (RT-PCR) and Sanger sequencing. Late and multiple local recurrences occurred in the atypical TGCTs, while no recurrences were reported in the conventional TGCTs. Our findings reveal that atypical TGCTs harbor gene fusions not implicating CSF1 and suggest that non-CSF1 fusions potentially confer greater propensity to recurrences and local aggressiveness while indicating the presence of alternate pathogenic mechanisms that warrant further investigation. MDPI 2019-12-31 /pmc/articles/PMC7016751/ /pubmed/31906059 http://dx.doi.org/10.3390/cancers12010100 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vougiouklakis, Theodore
Shen, Guomiao
Feng, Xiaojun
Hoda, Syed T.
Jour, George
Molecular Profiling of Atypical Tenosynovial Giant Cell Tumors Reveals Novel Non-CSF1 Fusions
title Molecular Profiling of Atypical Tenosynovial Giant Cell Tumors Reveals Novel Non-CSF1 Fusions
title_full Molecular Profiling of Atypical Tenosynovial Giant Cell Tumors Reveals Novel Non-CSF1 Fusions
title_fullStr Molecular Profiling of Atypical Tenosynovial Giant Cell Tumors Reveals Novel Non-CSF1 Fusions
title_full_unstemmed Molecular Profiling of Atypical Tenosynovial Giant Cell Tumors Reveals Novel Non-CSF1 Fusions
title_short Molecular Profiling of Atypical Tenosynovial Giant Cell Tumors Reveals Novel Non-CSF1 Fusions
title_sort molecular profiling of atypical tenosynovial giant cell tumors reveals novel non-csf1 fusions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016751/
https://www.ncbi.nlm.nih.gov/pubmed/31906059
http://dx.doi.org/10.3390/cancers12010100
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