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Expanding the molecular spectrum of tenosynovial giant cell tumors

BACKGROUND: While great advances in clinical and pathological description of tenosynovial giant cell tumors (TGCT) have been made, TGCT molecular heterogeneity represents an ongoing challenge. The canonical oncogenic fusion CSF1::COL6A3 is not systematically observed, suggesting that other oncogenic...

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Autores principales: Gauduchon, Thibault, Vanacker, Helene, Pissaloux, Daniel, Cassier, Philippe, Dufresne, Armelle, Karanian, Marie, Meurgey, Alexandra, Bouhamama, Amine, Gouin, François, Ray-Coquard, Isabelle, Blay, Jean-Yves, Tirode, Franck, Brahmi, Mehdi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691341/
https://www.ncbi.nlm.nih.gov/pubmed/36439507
http://dx.doi.org/10.3389/fonc.2022.1012527
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author Gauduchon, Thibault
Vanacker, Helene
Pissaloux, Daniel
Cassier, Philippe
Dufresne, Armelle
Karanian, Marie
Meurgey, Alexandra
Bouhamama, Amine
Gouin, François
Ray-Coquard, Isabelle
Blay, Jean-Yves
Tirode, Franck
Brahmi, Mehdi
author_facet Gauduchon, Thibault
Vanacker, Helene
Pissaloux, Daniel
Cassier, Philippe
Dufresne, Armelle
Karanian, Marie
Meurgey, Alexandra
Bouhamama, Amine
Gouin, François
Ray-Coquard, Isabelle
Blay, Jean-Yves
Tirode, Franck
Brahmi, Mehdi
author_sort Gauduchon, Thibault
collection PubMed
description BACKGROUND: While great advances in clinical and pathological description of tenosynovial giant cell tumors (TGCT) have been made, TGCT molecular heterogeneity represents an ongoing challenge. The canonical oncogenic fusion CSF1::COL6A3 is not systematically observed, suggesting that other oncogenic mechanisms are involved in tumorigenesis. This study aims to explore by RNA sequencing a retrospective series of tumors diagnosed as TGCT, in order to provide a better description of their molecular landscape and to correlate molecular features with clinical data. METHODS: We analyzed clinicopathological data and performed whole-exome RNA sequencing on 41 TGCT samples. RESULTS: RNAseq analysis showed significant higher CSF1 and CSF1-R expression than a control panel of 2642 solid tumors. RNA sequencing revealed fusion transcripts in 14 patients including 6 not involving CSF1 and some previously unreported fusions. Unsupervised clustering on the expression profiles issued from this series suggested two distinct subgroups: one composed of various molecular subtypes including CSF1 and FN1 rearranged samples and one composed of four tumors harboring an HMGA2::NCOR2 fusion, suggesting distinct tumor entities. Overall, 15 patients received at least one systemic anti-CSF1R treatment and clinical improvement was observed in 11 patients, including patients from both clusters. DISCUSSION: This study reported molecular heterogeneity in TGCT, contrasting with the clinical and pathological homogeneity and the ubiquitous high CSF1 and CSF1R expression levels. Whether molecular diversity may impact the efficacy of systemic treatments needs to be further investigated.
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spelling pubmed-96913412022-11-25 Expanding the molecular spectrum of tenosynovial giant cell tumors Gauduchon, Thibault Vanacker, Helene Pissaloux, Daniel Cassier, Philippe Dufresne, Armelle Karanian, Marie Meurgey, Alexandra Bouhamama, Amine Gouin, François Ray-Coquard, Isabelle Blay, Jean-Yves Tirode, Franck Brahmi, Mehdi Front Oncol Oncology BACKGROUND: While great advances in clinical and pathological description of tenosynovial giant cell tumors (TGCT) have been made, TGCT molecular heterogeneity represents an ongoing challenge. The canonical oncogenic fusion CSF1::COL6A3 is not systematically observed, suggesting that other oncogenic mechanisms are involved in tumorigenesis. This study aims to explore by RNA sequencing a retrospective series of tumors diagnosed as TGCT, in order to provide a better description of their molecular landscape and to correlate molecular features with clinical data. METHODS: We analyzed clinicopathological data and performed whole-exome RNA sequencing on 41 TGCT samples. RESULTS: RNAseq analysis showed significant higher CSF1 and CSF1-R expression than a control panel of 2642 solid tumors. RNA sequencing revealed fusion transcripts in 14 patients including 6 not involving CSF1 and some previously unreported fusions. Unsupervised clustering on the expression profiles issued from this series suggested two distinct subgroups: one composed of various molecular subtypes including CSF1 and FN1 rearranged samples and one composed of four tumors harboring an HMGA2::NCOR2 fusion, suggesting distinct tumor entities. Overall, 15 patients received at least one systemic anti-CSF1R treatment and clinical improvement was observed in 11 patients, including patients from both clusters. DISCUSSION: This study reported molecular heterogeneity in TGCT, contrasting with the clinical and pathological homogeneity and the ubiquitous high CSF1 and CSF1R expression levels. Whether molecular diversity may impact the efficacy of systemic treatments needs to be further investigated. Frontiers Media S.A. 2022-11-10 /pmc/articles/PMC9691341/ /pubmed/36439507 http://dx.doi.org/10.3389/fonc.2022.1012527 Text en Copyright © 2022 Gauduchon, Vanacker, Pissaloux, Cassier, Dufresne, Karanian, Meurgey, Bouhamama, Gouin, Ray-Coquard, Blay, Tirode and Brahmi 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
Gauduchon, Thibault
Vanacker, Helene
Pissaloux, Daniel
Cassier, Philippe
Dufresne, Armelle
Karanian, Marie
Meurgey, Alexandra
Bouhamama, Amine
Gouin, François
Ray-Coquard, Isabelle
Blay, Jean-Yves
Tirode, Franck
Brahmi, Mehdi
Expanding the molecular spectrum of tenosynovial giant cell tumors
title Expanding the molecular spectrum of tenosynovial giant cell tumors
title_full Expanding the molecular spectrum of tenosynovial giant cell tumors
title_fullStr Expanding the molecular spectrum of tenosynovial giant cell tumors
title_full_unstemmed Expanding the molecular spectrum of tenosynovial giant cell tumors
title_short Expanding the molecular spectrum of tenosynovial giant cell tumors
title_sort expanding the molecular spectrum of tenosynovial giant cell tumors
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691341/
https://www.ncbi.nlm.nih.gov/pubmed/36439507
http://dx.doi.org/10.3389/fonc.2022.1012527
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