In recent years, undifferentiated small round cell sarcomas (USRCSs) have been divided into a variety of new, rare, sarcoma subtypes, including the group of Ewing-like sarcomas, which have the morphological appearance of Ewing sarcomas, but carry CIC–DUX4, BCOR–CCNB3 and other gene fusions different from the classic EWSR1–ETS gene fusion. Using high-throughput RNA-sequencing (RNA-seq) analyses, we identified a novel recurrent gene fusion, CRTC1–SS18, in two cases of USRCS that lacked any known translocation. RNA-seq results were confirmed by reverse transcription polymerase chain reaction, long-range polymerase chain reaction, and fluorescence in situ hybridization. In vitro, we showed that the cells expressing the gene fusion were morphologically distinct and had enhanced oncogenic potential as compared with control cells. Expression profile comparisons with tumours of other sarcoma subtypes demonstrated that both cases clustered close to EWSR1–CREB1-positive tumours. Moreover, these analyses indicated enhanced NTRK1 expression in CRTC1–SS18-positive tumours. We conclude that the novel gene fusion identified in this study adds a new subtype to the USRCSs with unique gene signatures, and may be of therapeutic relevance.
Genetic analyses of undifferentiated small round cell sarcoma identifies a novel sarcoma subtype with a recurrent CRTC1-SS18 gene fusion / A. Alholle, M. Karanian, A.T. Brini, M.R. Morris, V. Kannappan, S. Niada, A. Niblett, D. Ranchère-Vince, D. Pissaloux, C. Delfour, A. Maran-Gonzalez, C.R. Antonescu, V. Sumathi, F. Tirode, F. Latif. - In: JOURNAL OF PATHOLOGY. - ISSN 0022-3417. - 245:2(2018 Jun), pp. 186-196.
|Titolo:||Genetic analyses of undifferentiated small round cell sarcoma identifies a novel sarcoma subtype with a recurrent CRTC1-SS18 gene fusion|
BRINI, ANNA TERESA (Secondo)
|Parole Chiave:||Ewing sarcoma; gene fusion; RNA-seq; undifferentiated small round cell sarcoma; 2734|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
Settore BIO/18 - Genetica
|Data di pubblicazione:||giu-2018|
|Data ahead of print / Data di stampa:||13-mar-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/path.5071|
|Appare nelle tipologie:||01 - Articolo su periodico|