Cargando…

NTRK‐rearranged spindle cell neoplasms are ubiquitous tumours of myofibroblastic lineage with a distinct methylation class

AIMS: NTRK gene fusions have been described in a wide variety of central nervous system (CNS) and soft tissue tumours, including the provisional tumour type ‘spindle cell neoplasm, NTRK‐rearranged’ (SCN–NTRK), added to the 2020 World Health Organisation Classification of Soft Tissue Tumours. Because...

Descripción completa

Detalles Bibliográficos
Autores principales: Tauziède‐Espariat, Arnault, Duchesne, Mathilde, Baud, Jessica, Le Quang, Mégane, Bochaton, Dorian, Azmani, Rihab, Croce, Sabrina, Hostein, Isabelle, Kesrouani, Carole, Guillemot, Delphine, Pierron, Gaëlle, Bourdeaut, Franck, Cardoen, Liesbeth, Hasty, Lauren, Lechapt, Emmanuèle, Métais, Alice, Chrétien, Fabrice, Puget, Stéphanie, Varlet, Pascale, Le Loarer, François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10108022/
https://www.ncbi.nlm.nih.gov/pubmed/36413100
http://dx.doi.org/10.1111/his.14842
_version_ 1785026749644406784
author Tauziède‐Espariat, Arnault
Duchesne, Mathilde
Baud, Jessica
Le Quang, Mégane
Bochaton, Dorian
Azmani, Rihab
Croce, Sabrina
Hostein, Isabelle
Kesrouani, Carole
Guillemot, Delphine
Pierron, Gaëlle
Bourdeaut, Franck
Cardoen, Liesbeth
Hasty, Lauren
Lechapt, Emmanuèle
Métais, Alice
Chrétien, Fabrice
Puget, Stéphanie
Varlet, Pascale
Le Loarer, François
author_facet Tauziède‐Espariat, Arnault
Duchesne, Mathilde
Baud, Jessica
Le Quang, Mégane
Bochaton, Dorian
Azmani, Rihab
Croce, Sabrina
Hostein, Isabelle
Kesrouani, Carole
Guillemot, Delphine
Pierron, Gaëlle
Bourdeaut, Franck
Cardoen, Liesbeth
Hasty, Lauren
Lechapt, Emmanuèle
Métais, Alice
Chrétien, Fabrice
Puget, Stéphanie
Varlet, Pascale
Le Loarer, François
author_sort Tauziède‐Espariat, Arnault
collection PubMed
description AIMS: NTRK gene fusions have been described in a wide variety of central nervous system (CNS) and soft tissue tumours, including the provisional tumour type ‘spindle cell neoplasm, NTRK‐rearranged’ (SCN–NTRK), added to the 2020 World Health Organisation Classification of Soft Tissue Tumours. Because of histopathological and molecular overlaps with other soft tissue entities, controversy remains concerning the lineage and terminology of SCN–NTRK. METHODS AND RESULTS: This study included 16 mesenchymal tumours displaying kinase gene fusions (NTRK fusions and one MET fusion) initially diagnosed as infantile fibrosarcomas (IFS), SCN–NTRK and adult‐type fibrosarcomas from the soft tissue, viscera and CNS. We used immunohistochemistry, DNA methylation profiling, whole RNA‐sequencing and ultrastructural analysis to characterise them. Unsupervised t‐distributed stochastic neighbour embedding analysis showed that 11 cases (two CNS tumours and nine extra‐CNS) formed a unique and new methylation cluster, while all tumours but one, initially diagnosed as IFS, clustered in a distinct methylation class. All the tumours except one formed a single cluster within the hierarchical clustering of whole RNA‐sequencing data. Tumours from the novel methylation class co‐expressed CD34 and S100, had variable histopathological grades and frequently displayed a CDKN2A deletion. Ultrastructural analyses evidenced a myofibroblastic differentiation. CONCLUSIONS: Our findings confirm that SCN‐NTRK share similar features in adults and children and in all locations combine an infiltrative pattern, distinct epigenetic and transcriptomic profiles, and ultrastructural evidence of a myofibroblastic lineage. Further studies may support the use of new terminology to better describe their myofibroblastic nature.
format Online
Article
Text
id pubmed-10108022
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-101080222023-04-18 NTRK‐rearranged spindle cell neoplasms are ubiquitous tumours of myofibroblastic lineage with a distinct methylation class Tauziède‐Espariat, Arnault Duchesne, Mathilde Baud, Jessica Le Quang, Mégane Bochaton, Dorian Azmani, Rihab Croce, Sabrina Hostein, Isabelle Kesrouani, Carole Guillemot, Delphine Pierron, Gaëlle Bourdeaut, Franck Cardoen, Liesbeth Hasty, Lauren Lechapt, Emmanuèle Métais, Alice Chrétien, Fabrice Puget, Stéphanie Varlet, Pascale Le Loarer, François Histopathology Original Articles AIMS: NTRK gene fusions have been described in a wide variety of central nervous system (CNS) and soft tissue tumours, including the provisional tumour type ‘spindle cell neoplasm, NTRK‐rearranged’ (SCN–NTRK), added to the 2020 World Health Organisation Classification of Soft Tissue Tumours. Because of histopathological and molecular overlaps with other soft tissue entities, controversy remains concerning the lineage and terminology of SCN–NTRK. METHODS AND RESULTS: This study included 16 mesenchymal tumours displaying kinase gene fusions (NTRK fusions and one MET fusion) initially diagnosed as infantile fibrosarcomas (IFS), SCN–NTRK and adult‐type fibrosarcomas from the soft tissue, viscera and CNS. We used immunohistochemistry, DNA methylation profiling, whole RNA‐sequencing and ultrastructural analysis to characterise them. Unsupervised t‐distributed stochastic neighbour embedding analysis showed that 11 cases (two CNS tumours and nine extra‐CNS) formed a unique and new methylation cluster, while all tumours but one, initially diagnosed as IFS, clustered in a distinct methylation class. All the tumours except one formed a single cluster within the hierarchical clustering of whole RNA‐sequencing data. Tumours from the novel methylation class co‐expressed CD34 and S100, had variable histopathological grades and frequently displayed a CDKN2A deletion. Ultrastructural analyses evidenced a myofibroblastic differentiation. CONCLUSIONS: Our findings confirm that SCN‐NTRK share similar features in adults and children and in all locations combine an infiltrative pattern, distinct epigenetic and transcriptomic profiles, and ultrastructural evidence of a myofibroblastic lineage. Further studies may support the use of new terminology to better describe their myofibroblastic nature. John Wiley and Sons Inc. 2022-12-12 2023-03 /pmc/articles/PMC10108022/ /pubmed/36413100 http://dx.doi.org/10.1111/his.14842 Text en © 2022 The Authors. Histopathology published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Tauziède‐Espariat, Arnault
Duchesne, Mathilde
Baud, Jessica
Le Quang, Mégane
Bochaton, Dorian
Azmani, Rihab
Croce, Sabrina
Hostein, Isabelle
Kesrouani, Carole
Guillemot, Delphine
Pierron, Gaëlle
Bourdeaut, Franck
Cardoen, Liesbeth
Hasty, Lauren
Lechapt, Emmanuèle
Métais, Alice
Chrétien, Fabrice
Puget, Stéphanie
Varlet, Pascale
Le Loarer, François
NTRK‐rearranged spindle cell neoplasms are ubiquitous tumours of myofibroblastic lineage with a distinct methylation class
title NTRK‐rearranged spindle cell neoplasms are ubiquitous tumours of myofibroblastic lineage with a distinct methylation class
title_full NTRK‐rearranged spindle cell neoplasms are ubiquitous tumours of myofibroblastic lineage with a distinct methylation class
title_fullStr NTRK‐rearranged spindle cell neoplasms are ubiquitous tumours of myofibroblastic lineage with a distinct methylation class
title_full_unstemmed NTRK‐rearranged spindle cell neoplasms are ubiquitous tumours of myofibroblastic lineage with a distinct methylation class
title_short NTRK‐rearranged spindle cell neoplasms are ubiquitous tumours of myofibroblastic lineage with a distinct methylation class
title_sort ntrk‐rearranged spindle cell neoplasms are ubiquitous tumours of myofibroblastic lineage with a distinct methylation class
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10108022/
https://www.ncbi.nlm.nih.gov/pubmed/36413100
http://dx.doi.org/10.1111/his.14842
work_keys_str_mv AT tauziedeespariatarnault ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT duchesnemathilde ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT baudjessica ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT lequangmegane ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT bochatondorian ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT azmanirihab ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT crocesabrina ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT hosteinisabelle ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT kesrouanicarole ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT guillemotdelphine ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT pierrongaelle ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT bourdeautfranck ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT cardoenliesbeth ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT hastylauren ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT lechaptemmanuele ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT metaisalice ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT chretienfabrice ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT pugetstephanie ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT varletpascale ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass
AT leloarerfrancois ntrkrearrangedspindlecellneoplasmsareubiquitoustumoursofmyofibroblasticlineagewithadistinctmethylationclass