Intra‐ and extra‐cranial BCOR‐ITD tumours are separate entities within the BCOR‐rearranged family
Abstract BCOR‐ITD tumours form an emerging family of aggressive entities with an internal tandem duplication (ITD) in the last exon of the BCOR gene. The family includes cerebral tumours, termed central nervous system BCOR‐ITD (CNS BCOR‐ITD), and sarcomatous types described in the kidney as clear ce...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-05-01
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| Series: | The Journal of Pathology: Clinical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cjp2.255 |
| _version_ | 1818755314933039104 |
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| author | Yassine Bouchoucha Arnault Tauziède‐Espariat Arnaud Gauthier Delphine Guillemot Dorian Bochaton Julien Vibert Matthieu Carton Sarah Watson Sandrine Grossetête Chloé Quignot Daniel Orbach Nadège Corradini Gudrun Schleiermacher Franck Bourdeaut Marie Simbozel Christelle Dufour Véronique Minard‐Colin Mehdi Brahmi Franck Tirode Daniel Pissaloux Marie Karanian Marie‐Christine Machet Julien Masliah‐Planchon Olivier Delattre Liesbeth Cardoen Gaëlle Pierron François Doz |
| author_facet | Yassine Bouchoucha Arnault Tauziède‐Espariat Arnaud Gauthier Delphine Guillemot Dorian Bochaton Julien Vibert Matthieu Carton Sarah Watson Sandrine Grossetête Chloé Quignot Daniel Orbach Nadège Corradini Gudrun Schleiermacher Franck Bourdeaut Marie Simbozel Christelle Dufour Véronique Minard‐Colin Mehdi Brahmi Franck Tirode Daniel Pissaloux Marie Karanian Marie‐Christine Machet Julien Masliah‐Planchon Olivier Delattre Liesbeth Cardoen Gaëlle Pierron François Doz |
| author_sort | Yassine Bouchoucha |
| collection | DOAJ |
| description | Abstract BCOR‐ITD tumours form an emerging family of aggressive entities with an internal tandem duplication (ITD) in the last exon of the BCOR gene. The family includes cerebral tumours, termed central nervous system BCOR‐ITD (CNS BCOR‐ITD), and sarcomatous types described in the kidney as clear cell sarcoma of the kidney (CCSK), in the endometrium as high‐grade endometrial stromal sarcoma, and in the bone and soft tissue as undifferentiated round cell sarcoma or primitive myxoid mesenchymal tumour of infancy. Based on a series of 33 retrospective cases, including 10 CNS BCOR‐ITD and 23 BCOR‐ITD sarcomas, we interrogated the homogeneity of the entity regarding clinical, radiological, and histopathological findings, and molecular signatures. Whole‐transcriptomic sequencing and DNA methylation profiling were used for unsupervised clustering. BCOR‐ITD tumours mostly affected young children with a median age at diagnosis of 2.1 years (range 0–62.4). Median overall survival was 3.9 years and progression‐free survival was 1.4 years. This dismal prognosis is shared among tumours in all locations except CCSK. Histopathological review revealed marked differences between CNS BCOR‐ITD and BCOR‐ITD sarcomas. These two groups were consistently segregated by unsupervised clustering of expression (n = 22) and DNA methylation (n = 21) data. Proximity between the two groups may result from common somatic changes within key pathways directly related to the novel activity of the ITD itself. Conversely, comparison of gene signatures with single‐cell RNA‐Seq atlases suggests that the distinction between BCOR‐ITD sarcomas and CNS BCOR‐ITD may result from differences in cells of origin. |
| first_indexed | 2024-12-18T05:37:11Z |
| format | Article |
| id | doaj.art-e02a318f290e402595038192d567159c |
| institution | Directory Open Access Journal |
| issn | 2056-4538 |
| language | English |
| last_indexed | 2024-12-18T05:37:11Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Journal of Pathology: Clinical Research |
| spelling | doaj.art-e02a318f290e402595038192d567159c2022-12-21T21:19:17ZengWileyThe Journal of Pathology: Clinical Research2056-45382022-05-018321723210.1002/cjp2.255Intra‐ and extra‐cranial BCOR‐ITD tumours are separate entities within the BCOR‐rearranged familyYassine Bouchoucha0Arnault Tauziède‐Espariat1Arnaud Gauthier2Delphine Guillemot3Dorian Bochaton4Julien Vibert5Matthieu Carton6Sarah Watson7Sandrine Grossetête8Chloé Quignot9Daniel Orbach10Nadège Corradini11Gudrun Schleiermacher12Franck Bourdeaut13Marie Simbozel14Christelle Dufour15Véronique Minard‐Colin16Mehdi Brahmi17Franck Tirode18Daniel Pissaloux19Marie Karanian20Marie‐Christine Machet21Julien Masliah‐Planchon22Olivier Delattre23Liesbeth Cardoen24Gaëlle Pierron25François Doz26SIREDO Oncology Center of Care, Innovation and Research for Children, Adolescent and Young Adults with Cancer Institut Curie Paris FranceUniversité de Paris Paris FranceDepartment of Pathology Institut Curie Paris FranceDepartment of Somatic Genetics Institut Curie Paris FranceLaboratory of Genetics and Biology of Cancer INSERM U830 Paris FranceLaboratory of Genetics and Biology of Cancer INSERM U830 Paris FranceDepartment of Biostatistics Institut Curie Paris FranceLaboratory of Genetics and Biology of Cancer INSERM U830 Paris FranceLaboratory of Genetics and Biology of Cancer INSERM U830 Paris FranceLaboratory of Genetics and Biology of Cancer INSERM U830 Paris FranceSIREDO Oncology Center of Care, Innovation and Research for Children, Adolescent and Young Adults with Cancer Institut Curie Paris FranceInstitute of Pediatric Hematology and Oncology IHOPE Centre Leon Berard Lyon FranceSIREDO Oncology Center of Care, Innovation and Research for Children, Adolescent and Young Adults with Cancer Institut Curie Paris FranceSIREDO Oncology Center of Care, Innovation and Research for Children, Adolescent and Young Adults with Cancer Institut Curie Paris FranceDepartment of Pediatric and Adolescent Oncology INSERM 1015, Gustave Roussy, Paris‐Saclay University Villejuif FranceDepartment of Pediatric and Adolescent Oncology INSERM 1015, Gustave Roussy, Paris‐Saclay University Villejuif FranceDepartment of Pediatric and Adolescent Oncology INSERM 1015, Gustave Roussy, Paris‐Saclay University Villejuif FranceGenetics Epigenetics and Biology of Sarcomas Team Claude Bernard University Lyon 1, INSERM 1052, CNRS 5286, Cancer Research Center of Lyon, Centre Léon Bérard Lyon FranceGenetics Epigenetics and Biology of Sarcomas Team Claude Bernard University Lyon 1, INSERM 1052, CNRS 5286, Cancer Research Center of Lyon, Centre Léon Bérard Lyon FranceGenetics Epigenetics and Biology of Sarcomas Team Claude Bernard University Lyon 1, INSERM 1052, CNRS 5286, Cancer Research Center of Lyon, Centre Léon Bérard Lyon FranceGenetics Epigenetics and Biology of Sarcomas Team Claude Bernard University Lyon 1, INSERM 1052, CNRS 5286, Cancer Research Center of Lyon, Centre Léon Bérard Lyon FranceDepartment of Pathology CHRU Bretonneau Tours FranceDepartment of Somatic Genetics Institut Curie Paris FranceSIREDO Oncology Center of Care, Innovation and Research for Children, Adolescent and Young Adults with Cancer Institut Curie Paris FranceImaging Department Institut Curie Paris FranceDepartment of Somatic Genetics Institut Curie Paris FranceSIREDO Oncology Center of Care, Innovation and Research for Children, Adolescent and Young Adults with Cancer Institut Curie Paris FranceAbstract BCOR‐ITD tumours form an emerging family of aggressive entities with an internal tandem duplication (ITD) in the last exon of the BCOR gene. The family includes cerebral tumours, termed central nervous system BCOR‐ITD (CNS BCOR‐ITD), and sarcomatous types described in the kidney as clear cell sarcoma of the kidney (CCSK), in the endometrium as high‐grade endometrial stromal sarcoma, and in the bone and soft tissue as undifferentiated round cell sarcoma or primitive myxoid mesenchymal tumour of infancy. Based on a series of 33 retrospective cases, including 10 CNS BCOR‐ITD and 23 BCOR‐ITD sarcomas, we interrogated the homogeneity of the entity regarding clinical, radiological, and histopathological findings, and molecular signatures. Whole‐transcriptomic sequencing and DNA methylation profiling were used for unsupervised clustering. BCOR‐ITD tumours mostly affected young children with a median age at diagnosis of 2.1 years (range 0–62.4). Median overall survival was 3.9 years and progression‐free survival was 1.4 years. This dismal prognosis is shared among tumours in all locations except CCSK. Histopathological review revealed marked differences between CNS BCOR‐ITD and BCOR‐ITD sarcomas. These two groups were consistently segregated by unsupervised clustering of expression (n = 22) and DNA methylation (n = 21) data. Proximity between the two groups may result from common somatic changes within key pathways directly related to the novel activity of the ITD itself. Conversely, comparison of gene signatures with single‐cell RNA‐Seq atlases suggests that the distinction between BCOR‐ITD sarcomas and CNS BCOR‐ITD may result from differences in cells of origin.https://doi.org/10.1002/cjp2.255CNS BCOR‐ITDBCOR‐ITD sarcomasCCSKESSclusteringtranscriptome |
| spellingShingle | Yassine Bouchoucha Arnault Tauziède‐Espariat Arnaud Gauthier Delphine Guillemot Dorian Bochaton Julien Vibert Matthieu Carton Sarah Watson Sandrine Grossetête Chloé Quignot Daniel Orbach Nadège Corradini Gudrun Schleiermacher Franck Bourdeaut Marie Simbozel Christelle Dufour Véronique Minard‐Colin Mehdi Brahmi Franck Tirode Daniel Pissaloux Marie Karanian Marie‐Christine Machet Julien Masliah‐Planchon Olivier Delattre Liesbeth Cardoen Gaëlle Pierron François Doz Intra‐ and extra‐cranial BCOR‐ITD tumours are separate entities within the BCOR‐rearranged family The Journal of Pathology: Clinical Research CNS BCOR‐ITD BCOR‐ITD sarcomas CCSK ESS clustering transcriptome |
| title | Intra‐ and extra‐cranial BCOR‐ITD tumours are separate entities within the BCOR‐rearranged family |
| title_full | Intra‐ and extra‐cranial BCOR‐ITD tumours are separate entities within the BCOR‐rearranged family |
| title_fullStr | Intra‐ and extra‐cranial BCOR‐ITD tumours are separate entities within the BCOR‐rearranged family |
| title_full_unstemmed | Intra‐ and extra‐cranial BCOR‐ITD tumours are separate entities within the BCOR‐rearranged family |
| title_short | Intra‐ and extra‐cranial BCOR‐ITD tumours are separate entities within the BCOR‐rearranged family |
| title_sort | intra and extra cranial bcor itd tumours are separate entities within the bcor rearranged family |
| topic | CNS BCOR‐ITD BCOR‐ITD sarcomas CCSK ESS clustering transcriptome |
| url | https://doi.org/10.1002/cjp2.255 |
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