{"doi":"10.3389/fonc.2022.1012527","title":"Expanding the molecular spectrum of tenosynovial giant cell tumors","abstract":"<jats:sec><jats:title>Background</jats:title><jats:p>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 <jats:italic>CSF1::COL6A3</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We analyzed clinicopathological data and performed whole-exome RNA sequencing on 41 TGCT samples.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 <jats:italic>CSF1</jats:italic> and <jats:italic>FN1</jats:italic> rearranged samples and one composed of four tumors harboring an <jats:italic>HMGA2::NCOR2</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>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.</jats:p></jats:sec>","journal":"Frontiers in Oncology","year":2022,"id":646168,"datarank":0.4566783656585135,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.0,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1682877,"name":"Helene Vanacker","orcid":null,"position":1,"is_corresponding":false},{"id":314866,"name":"Daniel Pissaloux","orcid":"0000-0003-1118-950X","position":2,"is_corresponding":false},{"id":1530806,"name":"Philippe Cassier","orcid":null,"position":3,"is_corresponding":false},{"id":1682878,"name":"Armelle Dufresne","orcid":null,"position":4,"is_corresponding":false},{"id":1682879,"name":"Marie Karanian","orcid":null,"position":5,"is_corresponding":false},{"id":1682880,"name":"Alexandra Meurgey","orcid":null,"position":6,"is_corresponding":false},{"id":1682881,"name":"Amine Bouhamama","orcid":null,"position":7,"is_corresponding":false},{"id":1682882,"name":"François Gouin","orcid":null,"position":8,"is_corresponding":false},{"id":50152,"name":"Isabelle Ray-Coquard","orcid":null,"position":9,"is_corresponding":false},{"id":619569,"name":"Jean-Yves Blay","orcid":null,"position":10,"is_corresponding":false},{"id":314863,"name":"Franck Tirode","orcid":"0000-0003-4731-7817","position":11,"is_corresponding":false},{"id":1682883,"name":"Mehdi Brahmi","orcid":null,"position":12,"is_corresponding":false},{"id":1682876,"name":"Thibault Gauduchon","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Expanding the molecular spectrum of tenosynovial giant cell tumors","abstract":"<jats:sec><jats:title>Background</jats:title><jats:p>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 <jats:italic>CSF1::COL6A3</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We analyzed clinicopathological data and performed whole-exome RNA sequencing on 41 TGCT samples.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 <jats:italic>CSF1</jats:italic> and <jats:italic>FN1</jats:italic> rearranged samples and one composed of four tumors harboring an <jats:italic>HMGA2::NCOR2</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>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.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36439507","pmcid":"PMC9691341","openalex_id":null,"authors":[],"funders":[{"funder_name":"French National Research Agency (ANR)","grant_id":"ANR-10-LABX-0061","title":null},{"funder_name":"Institut National du Cancer","grant_id":"unidentified","title":"unidentified"},{"funder_name":"European Commission","grant_id":"278742","title":"European Clinical trials in Rare Sarcomas within an integrated translational trial network"},{"funder_name":"LabEx DEvweCAN","grant_id":"","title":null},{"funder_name":"Institut National Du Cancer","grant_id":"","title":null},{"funder_name":"Fondation ARC pour la Recherche sur le Cancer","grant_id":"","title":null}],"total_grants":6,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.3389/fonc.2022.1012527","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fonc.2022.1012527/full","host_type":"publisher"},{"url":"https://doaj.org/article/207e1292ce8e4d09892f6ace094f5615","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9691341","host_type":"repository"},{"url":"https://www.frontiersin.org/articles/10.3389/fonc.2022.1012527/pdf","host_type":"Unpaywall"},{"url":"https://europepmc.org/articles/PMC9691341","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9691341?pdf=render","host_type":"Europe_PMC"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36439507","host_type":""},{"url":"http://dx.doi.org/10.3389/fonc.2022.1012527","host_type":""},{"url":"https://cnrs.hal.science/hal-05002645v1","host_type":""}],"fields_of_study":["03 medical and health sciences","0302 clinical medicine"],"mesh_terms":[],"keywords":["Expression profile","Csf1","Gene Fusions","Rnaseq Analysis","Tenosynovial Giant Cell Tumor (Tgct)","Csf1 Fusion Transcript","Cancer Research","Neoplasms. 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