Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1783497047205216256 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7016751 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT vougiouklakistheodore molecularprofilingofatypicaltenosynovialgiantcelltumorsrevealsnovelnoncsf1fusions AT shenguomiao molecularprofilingofatypicaltenosynovialgiantcelltumorsrevealsnovelnoncsf1fusions AT fengxiaojun molecularprofilingofatypicaltenosynovialgiantcelltumorsrevealsnovelnoncsf1fusions AT hodasyedt molecularprofilingofatypicaltenosynovialgiantcelltumorsrevealsnovelnoncsf1fusions AT jourgeorge molecularprofilingofatypicaltenosynovialgiantcelltumorsrevealsnovelnoncsf1fusions |