Transcriptomic definition of molecular subgroups of small round cell sarcomas

Abstract

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.

KMT2A (MLL) fusions in aggressive sarcomas in young adults

“…Very recently, YAP1 – KMT2A fusion transcript was detected in a single unclassifiable sarcoma case in a large molecular series, and our report confirms that this fusion is recurrent in sarcoma. That case (SARC002) affected the chest wall of a 35‐year‐old woman; however, its histomorphology, immunophenotype and clinical course were undescribed.…”

The combination of radiotherapy and ALK inhibitors is effective in the treatment of intraosseous rhabdomyosarcoma with FUS‐TFCP2 fusion transcript

“…The TFCP2 gene rearrangement was confirmed by FISH analysis. These results support the diagnosis of an intra‐osseous FUS/TFCP2 RMS, a rare new entity recently described in the literature …”

“…Rhabdomyosarcoma (RMS), which mainly affects paediatric patients, is classified by the current World Health Organization into four major subtypes . Recently, a subgroup of highly aggressive intraosseous RMS demonstrated new fusion transcripts, involving a FET ‐family gene with TFCP2 . Very few cases have been reported in the literature and all demonstrated a poor prognosis .…”

Primary malignant epithelioid and rhabdoid tumor of bone harboring ZNF532‐NUTM1 fusion: the expanding NUT cancer family

“…[5][6][7][8][9][10][11][12][13] As the relationship between these tumors and conventional NC is still unclear, the classification terminology used in the literature varies, including NUT-associated tumors, 5 malignant epithelioid neoplasia, 7 NUT carcinomas, 11 and sarcomas. [5][6][7][8][9][11][12][13] In this study, we report a primary bone with ZNF592-NUTM1 fusion. [5][6][7][8][9][11][12][13] In this study, we report a primary bone with ZNF592-NUTM1 fusion.…”

“…2 With high sensitivity (87%) and specificity (100%), NUT immunostain has been utilized as a diagnostic substitute for molecular testing. [5][6][7][8][9][10][11][12][13] These tumors exhibit a wider and more heterogeneous morphologic spectrum compared to typical NC. 4 Recently, NUTM1 gene rearrangements have been increasingly identified in other cancers.…”