Transcriptomic definition of molecular subgroups of small round cell sarcomas
Sarah Watson
INSERM U830, Laboratory of Genetics and Biology of Cancer, Paris, France
Institut Curie, Paris Sciences et Lettres, Paris, France
Search for more papers by this authorVirginie Perrin
INSERM U830, Laboratory of Genetics and Biology of Cancer, Paris, France
Institut Curie, Paris Sciences et Lettres, Paris, France
Search for more papers by this authorDelphine Guillemot
Institut Curie, Unité de Génétique Somatique, Paris, France
Search for more papers by this authorStephanie Reynaud
Institut Curie, Unité de Génétique Somatique, Paris, France
Search for more papers by this authorJean-Michel Coindre
Institut Bergonié, Department of Pathology, Bordeaux, France
Université Bordeaux 2, Bordeaux, France
Search for more papers by this authorMarie Karanian
Centre Leon Bérard, Department of Pathology, Lyon, France
Search for more papers by this authorJean-Marc Guinebretière
Service de Pathologie, Hôpital René-Huguenin, Institut Curie, Saint-Cloud, France
Search for more papers by this authorPaul Freneaux
Département de Biologie des Tumeurs, Institut Curie, Service d'Anatomie Pathologique, Paris, France
Search for more papers by this authorFrançois Le Loarer
Institut Bergonié, Department of Pathology, Bordeaux, France
Université Bordeaux 2, Bordeaux, France
Search for more papers by this authorMegane Bouvet
Institut Curie, Unité de Génétique Somatique, Paris, France
Search for more papers by this authorLouise Galmiche-Rolland
Service d'Anatomie Pathologique, Hôpital Necker Enfants Malades, Paris, France
Université Paris Descartes, Paris, France
Search for more papers by this authorFrédérique Larousserie
Service d'Anatomie Pathologique, Hôpital Cochin, Paris, France
Search for more papers by this authorElisabeth Longchampt
Service d'Anatomie et de Cytologie Pathologiques, Hôpital Foch, Suresnes, France
Search for more papers by this authorDominique Ranchere-Vince
Centre Leon Bérard, Department of Pathology, Lyon, France
Search for more papers by this authorGaelle Pierron
Institut Curie, Unité de Génétique Somatique, Paris, France
Co-senior authors.Search for more papers by this authorCorresponding Author
Olivier Delattre
INSERM U830, Laboratory of Genetics and Biology of Cancer, Paris, France
Institut Curie, Paris Sciences et Lettres, Paris, France
Institut Curie, Unité de Génétique Somatique, Paris, France
Ligue Contre le Cancer, Equipe Labellisée
Co-senior authors.Correspondence to: Franck Tirode, PhD, Biology of Rare Sarcomas Group, Cancer Research Center of Lyon, INSERM U1052, Centre Léon Bérard, 28 Rue Laënnec, 69373 Lyon Cedex 08, France. E-mail: [email protected]; Or Olivier Delattre, MD, PhD, INSERM U830 ‘Genetics and Biology of Cancers’, Institut Curie Research Centre, 26 Rue d'Ulm, 75248 Paris Cedex 05, France. E-mail: [email protected]Search for more papers by this authorCorresponding Author
Franck Tirode
INSERM U830, Laboratory of Genetics and Biology of Cancer, Paris, France
Institut Curie, Paris Sciences et Lettres, Paris, France
Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Cancer Research Center of Lyon, Centre Léon Bérard, Lyon, France
Co-senior authors.Correspondence to: Franck Tirode, PhD, Biology of Rare Sarcomas Group, Cancer Research Center of Lyon, INSERM U1052, Centre Léon Bérard, 28 Rue Laënnec, 69373 Lyon Cedex 08, France. E-mail: [email protected]; Or Olivier Delattre, MD, PhD, INSERM U830 ‘Genetics and Biology of Cancers’, Institut Curie Research Centre, 26 Rue d'Ulm, 75248 Paris Cedex 05, France. E-mail: [email protected]Search for more papers by this authorSarah Watson
INSERM U830, Laboratory of Genetics and Biology of Cancer, Paris, France
Institut Curie, Paris Sciences et Lettres, Paris, France
Search for more papers by this authorVirginie Perrin
INSERM U830, Laboratory of Genetics and Biology of Cancer, Paris, France
Institut Curie, Paris Sciences et Lettres, Paris, France
Search for more papers by this authorDelphine Guillemot
Institut Curie, Unité de Génétique Somatique, Paris, France
Search for more papers by this authorStephanie Reynaud
Institut Curie, Unité de Génétique Somatique, Paris, France
Search for more papers by this authorJean-Michel Coindre
Institut Bergonié, Department of Pathology, Bordeaux, France
Université Bordeaux 2, Bordeaux, France
Search for more papers by this authorMarie Karanian
Centre Leon Bérard, Department of Pathology, Lyon, France
Search for more papers by this authorJean-Marc Guinebretière
Service de Pathologie, Hôpital René-Huguenin, Institut Curie, Saint-Cloud, France
Search for more papers by this authorPaul Freneaux
Département de Biologie des Tumeurs, Institut Curie, Service d'Anatomie Pathologique, Paris, France
Search for more papers by this authorFrançois Le Loarer
Institut Bergonié, Department of Pathology, Bordeaux, France
Université Bordeaux 2, Bordeaux, France
Search for more papers by this authorMegane Bouvet
Institut Curie, Unité de Génétique Somatique, Paris, France
Search for more papers by this authorLouise Galmiche-Rolland
Service d'Anatomie Pathologique, Hôpital Necker Enfants Malades, Paris, France
Université Paris Descartes, Paris, France
Search for more papers by this authorFrédérique Larousserie
Service d'Anatomie Pathologique, Hôpital Cochin, Paris, France
Search for more papers by this authorElisabeth Longchampt
Service d'Anatomie et de Cytologie Pathologiques, Hôpital Foch, Suresnes, France
Search for more papers by this authorDominique Ranchere-Vince
Centre Leon Bérard, Department of Pathology, Lyon, France
Search for more papers by this authorGaelle Pierron
Institut Curie, Unité de Génétique Somatique, Paris, France
Co-senior authors.Search for more papers by this authorCorresponding Author
Olivier Delattre
INSERM U830, Laboratory of Genetics and Biology of Cancer, Paris, France
Institut Curie, Paris Sciences et Lettres, Paris, France
Institut Curie, Unité de Génétique Somatique, Paris, France
Ligue Contre le Cancer, Equipe Labellisée
Co-senior authors.Correspondence to: Franck Tirode, PhD, Biology of Rare Sarcomas Group, Cancer Research Center of Lyon, INSERM U1052, Centre Léon Bérard, 28 Rue Laënnec, 69373 Lyon Cedex 08, France. E-mail: [email protected]; Or Olivier Delattre, MD, PhD, INSERM U830 ‘Genetics and Biology of Cancers’, Institut Curie Research Centre, 26 Rue d'Ulm, 75248 Paris Cedex 05, France. E-mail: [email protected]Search for more papers by this authorCorresponding Author
Franck Tirode
INSERM U830, Laboratory of Genetics and Biology of Cancer, Paris, France
Institut Curie, Paris Sciences et Lettres, Paris, France
Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Cancer Research Center of Lyon, Centre Léon Bérard, Lyon, France
Co-senior authors.Correspondence to: Franck Tirode, PhD, Biology of Rare Sarcomas Group, Cancer Research Center of Lyon, INSERM U1052, Centre Léon Bérard, 28 Rue Laënnec, 69373 Lyon Cedex 08, France. E-mail: [email protected]; Or Olivier Delattre, MD, PhD, INSERM U830 ‘Genetics and Biology of Cancers’, Institut Curie Research Centre, 26 Rue d'Ulm, 75248 Paris Cedex 05, France. E-mail: [email protected]Search for more papers by this authorAbstract
Sarcoma represents a highly heterogeneous group of tumours. We report here the first unbiased and systematic search for gene fusions combined with unsupervised expression analysis of a series of 184 small round cell sarcomas. Fusion genes were detected in 59% of samples, with half of them being observed recurrently. We identified biologically homogeneous groups of tumours such as the CIC-fused (to DUX4, FOXO4 or NUTM1) and BCOR-rearranged (BCOR–CCNB3, BCOR–MAML3, ZC3H7B–BCOR, and BCOR internal duplication) tumour groups. VGLL2-fused tumours represented a more biologically and pathologically heterogeneous group. This study also refined the characteristics of some entities such as EWSR1–PATZ1 spindle cell sarcoma or FUS–NFATC2 bone tumours that are different from EWSR1–NFATC2 tumours and transcriptionally resemble CIC-fused tumour entities. We also describe a completely novel group of epithelioid and spindle-cell rhabdomyosarcomas characterized by EWSR1– or FUS–TFCP2 fusions. Finally, expression data identified some potentially new therapeutic targets or pathways. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Supporting Information
| Filename | Description |
|---|---|
| path5053-sup-0001-SupInfo.pdfPDF document, 2.2 MB |
Figure S1. Constitution of the cohorts Figure S2. Detailed unsupervised analyses Figure S3. Details of VGLL2–NCOA2/CITED2, CIC–NUTM1, BCOR-ITD, and EWSR1–PATZ1 fusion points Figure S4. Sequence of the fusion points and genes expressed in FET–TFCP2-positive tumours Figure S5. Expression of the most specific gene for each tumor entity (with more than two samples) |
| path5053-sup-0002-TableS1.xlsExcel spreadsheet, 29 KB | Table S1. List of the fusion genes routinely tested by RT-PCR at the Institut Curie Unité de Génétique Somatique |
| path5053-sup-0003-TableS2.xlsExcel spreadsheet, 76.5 KB | Table S2. Description of the samples from the three cohorts |
| path5053-sup-0004-TableS3.xlsExcel spreadsheet, 3.1 MB | Table S3. Differentially expressed genes in the BGA and supervised analyses and Gene ontology/GSEA enrichment for all sarcomas subtypes |
| path5053-sup-0005-TableS4.xlsExcel spreadsheet, 228.5 KB | Table S4. Differentially expressed genes and gene ontology enrichment for FUS–NFATC2-positive versus EWSR1–NFATC2-positive tumours |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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