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Synovial chondromatosis and soft tissue chondroma: extra-osseous cartilaginous tumours defined by FN1 gene rearrangement
A fusion between fibronectin 1 (FN1) and activin receptor 2A (ACVR2A) has been reported previously in isolated cases of the synovial chondromatosis. To analyse further and validate the findings, we performed FISH and demonstrated recurrent FN1-ACVR2A rearrangements in synovial chondromatosis (57%),...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882679/ https://www.ncbi.nlm.nih.gov/pubmed/31273315 http://dx.doi.org/10.1038/s41379-019-0315-8 |
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author | Amary, Fernanda Perez-Casanova, Luis Ye, Hongtao Cottone, Lucia Strobl, Anna Cool, Paul Miranda, Elena Berisha, Fitim Aston, William Rocha, Maia O’Donnell, Paul Pillay, Nischalan Tirabosco, Roberto Baumhoer, Daniel Hookway, Edward S Flanagan, Adrienne M |
author_facet | Amary, Fernanda Perez-Casanova, Luis Ye, Hongtao Cottone, Lucia Strobl, Anna Cool, Paul Miranda, Elena Berisha, Fitim Aston, William Rocha, Maia O’Donnell, Paul Pillay, Nischalan Tirabosco, Roberto Baumhoer, Daniel Hookway, Edward S Flanagan, Adrienne M |
author_sort | Amary, Fernanda |
collection | PubMed |
description | A fusion between fibronectin 1 (FN1) and activin receptor 2A (ACVR2A) has been reported previously in isolated cases of the synovial chondromatosis. To analyse further and validate the findings, we performed FISH and demonstrated recurrent FN1-ACVR2A rearrangements in synovial chondromatosis (57%), and chondrosarcoma secondary to synovial chondromatosis (75%), showing that FN1 and/or AVCRA2 gene rearrangements do not distinguish between benign and malignant synovial chondromatosis. RNA sequencing revealed the presence of the FN1-ACVR2A fusion in several cases that were negative by FISH suggesting that the true prevalence of this fusion is potentially higher than 57%. In soft tissue chondromas, FN1 alterations were detected by FISH in 50% of cases but no ACVR2A alterations were identified. RNA sequencing identified a fusion involving FN1 and fibroblast growth factor receptor 2 (FGFR2) in a case of soft tissue chondroma and FISH confirmed recurrent involvement of both FGFR1 and FGFR2. These fusions were present in a subset of soft tissue chondromas characterised by grungy calcification a feature reminiscent of phosphaturic mesenchymal tumour. However, unlike the latter, fibroblast growth factor 23 (FGF23) mRNA expression was not elevated in soft tissue chondromas harbouring the FN1-FGFR1 fusion. The mutual exclusivity of ACVR2A rearrangements observed in synovial chondromatosis and FGFR1/2 in soft tissue chondromas suggests these represent separate entities. There have been no reports of malignant soft tissue chondromas, therefore differentiating these lesions will potentially alter clinical management by allowing soft tissue chondromas to be managed more conservatively. |
format | Online Article Text |
id | pubmed-6882679 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-68826792019-11-28 Synovial chondromatosis and soft tissue chondroma: extra-osseous cartilaginous tumours defined by FN1 gene rearrangement Amary, Fernanda Perez-Casanova, Luis Ye, Hongtao Cottone, Lucia Strobl, Anna Cool, Paul Miranda, Elena Berisha, Fitim Aston, William Rocha, Maia O’Donnell, Paul Pillay, Nischalan Tirabosco, Roberto Baumhoer, Daniel Hookway, Edward S Flanagan, Adrienne M Mod Pathol Article A fusion between fibronectin 1 (FN1) and activin receptor 2A (ACVR2A) has been reported previously in isolated cases of the synovial chondromatosis. To analyse further and validate the findings, we performed FISH and demonstrated recurrent FN1-ACVR2A rearrangements in synovial chondromatosis (57%), and chondrosarcoma secondary to synovial chondromatosis (75%), showing that FN1 and/or AVCRA2 gene rearrangements do not distinguish between benign and malignant synovial chondromatosis. RNA sequencing revealed the presence of the FN1-ACVR2A fusion in several cases that were negative by FISH suggesting that the true prevalence of this fusion is potentially higher than 57%. In soft tissue chondromas, FN1 alterations were detected by FISH in 50% of cases but no ACVR2A alterations were identified. RNA sequencing identified a fusion involving FN1 and fibroblast growth factor receptor 2 (FGFR2) in a case of soft tissue chondroma and FISH confirmed recurrent involvement of both FGFR1 and FGFR2. These fusions were present in a subset of soft tissue chondromas characterised by grungy calcification a feature reminiscent of phosphaturic mesenchymal tumour. However, unlike the latter, fibroblast growth factor 23 (FGF23) mRNA expression was not elevated in soft tissue chondromas harbouring the FN1-FGFR1 fusion. The mutual exclusivity of ACVR2A rearrangements observed in synovial chondromatosis and FGFR1/2 in soft tissue chondromas suggests these represent separate entities. There have been no reports of malignant soft tissue chondromas, therefore differentiating these lesions will potentially alter clinical management by allowing soft tissue chondromas to be managed more conservatively. 2019-06-14 2019-07-04 /pmc/articles/PMC6882679/ /pubmed/31273315 http://dx.doi.org/10.1038/s41379-019-0315-8 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Amary, Fernanda Perez-Casanova, Luis Ye, Hongtao Cottone, Lucia Strobl, Anna Cool, Paul Miranda, Elena Berisha, Fitim Aston, William Rocha, Maia O’Donnell, Paul Pillay, Nischalan Tirabosco, Roberto Baumhoer, Daniel Hookway, Edward S Flanagan, Adrienne M Synovial chondromatosis and soft tissue chondroma: extra-osseous cartilaginous tumours defined by FN1 gene rearrangement |
title | Synovial chondromatosis and soft tissue chondroma: extra-osseous cartilaginous tumours defined by FN1 gene rearrangement |
title_full | Synovial chondromatosis and soft tissue chondroma: extra-osseous cartilaginous tumours defined by FN1 gene rearrangement |
title_fullStr | Synovial chondromatosis and soft tissue chondroma: extra-osseous cartilaginous tumours defined by FN1 gene rearrangement |
title_full_unstemmed | Synovial chondromatosis and soft tissue chondroma: extra-osseous cartilaginous tumours defined by FN1 gene rearrangement |
title_short | Synovial chondromatosis and soft tissue chondroma: extra-osseous cartilaginous tumours defined by FN1 gene rearrangement |
title_sort | synovial chondromatosis and soft tissue chondroma: extra-osseous cartilaginous tumours defined by fn1 gene rearrangement |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882679/ https://www.ncbi.nlm.nih.gov/pubmed/31273315 http://dx.doi.org/10.1038/s41379-019-0315-8 |
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