Transcriptomic definition of molecular subgroups of small round cell sarcomas

Sarah Watson (1, 2) , Virginie Perrin (1, 2) , Delphine Guillemot (3) , Stéphanie Reynaud (2) , Jean-Michel Coindre (4, 5) , Marie Karanian (6) , Jean-Marc Guinebretière (7, 2) , Paul Fréneaux (2) , Francois Le Loarer (4, 5) , Megane Bouvet (3) , Louise Galmiche-Rolland (8, 9) , Frédérique Larousserie (10) , Elisabeth Longchampt (11) , Dominique Ranchère-Vince (6) , Gaëlle Pierron (3) , Olivier Delattre (1, 3, 12) , Franck Tirode (13, 1, 2)

1 U830 - Unité de génétique et biologie des cancers
2 Institut Curie [Paris]
3 Unité de Génétique Somatique
4 Institut Bergonié [Bordeaux]
5 UB - Université de Bordeaux
6 Centre Léon Bérard [Lyon]
7 Hôpital René Huguenin [Saint-Cloud]
8 Service de pathologie [CHU Necker]
9 UPD5 - Université Paris Descartes - Paris 5
10 Hôpital Cochin [AP-HP]
11 Hôpital Foch [Suresnes]
12 Equipe labellisée Ligue contre le Cancer
13 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon

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.

Mots clés: VGLL2-NCOA2; fusion genes; sarcoma; RNAseq; FUS-NFATC2; FET-TFCP2; EWSR1-PATZ1; CIC-fused; BCOR-rearranged

Domaines: Cancer; Génomique, Transcriptomique et Protéomique [q-bio.GN]; Biologie moléculaire

Sarah Watson, Virginie Perrin, Delphine Guillemot, Stéphanie Reynaud, Jean-Michel Coindre, et al.. Transcriptomic definition of molecular subgroups of small round cell sarcomas. The Journal of pathology and bacteriology, 2018, 245 (1), pp.29-40. ⟨10.1002/path.5053⟩. ⟨inserm-02440510⟩