Genetic analyses of undifferentiated small round cell sarcoma identifies a novel sarcoma subtype with a recurrent CRTC1-SS18 gene fusion

Abstract

In recent years, undifferentiated small round cell sarcoma (USRCS) have been divided into a variety of new, rare, sarcoma subtypes including the group of Ewing-like sarcoma that has the morphological appearance of Ewing sarcoma but carries CIC-DUX4, BCOR-CCNB3 and other gene fusions different from the classical EWSR1-ETS. Using high-throughput 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 RT-PCR, long-range PCR and FISH. In vitro, we show that the cells expressing the gene fusion were morphologically distinct and demonstrated enhanced oncogenic potential compared to 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 an 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 USRCS with unique gene signatures and maybe of therapeutic relevance.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FyfZmB