Abstract 253: Identification of novel EWSR1-CREB3L1 fusion transcript in small cell osteosarcoma

Abstract

Abstract Small cell osteosarcoma (SCOS) is an aggressive variant of osteogenic sarcoma that has some morphologic similarities to Ewing sarcoma. Little is known about the molecular biology of SCOS and no specific molecular abnormality has been reported in this tumor subtype to date. We performed a molecular biology study of a SCOS that was positive for the Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement by interphase fluorescent in situ hybridization and negative for EWSR1-FLI1, EWSR1-ERG and EWSR1-WT1 fusion transcripts by reverse transcriptase polymerase chain reaction. Rapid amplification of cDNA ends with the EWSR1 gene-specific forward primers revealed the exon 6 of the cAMP responsive element binding protein 3-like 1 gene (CREB3L1) fused in-frame to the EWSR1 exon 11, consistent with the EWSR1-CREB2L1 fusion transcript expressed in tumor tissue. The corresponding chimeric gene in the tumor DNA was confirmed by amplification and subsequent sequencing of the genetic breakpoint located in introns 11 and 5 of the EWSR1 and CREB3L1, respectively. No reciprocal fusion transcript or gene could be amplified in the tumor. An approximately 68 kDa product detected in tumor tissue lysate by immunoblotting with the CREB3L1 carboxyterminal antibody was consistent with a 656 aa predicted chimeric protein. This is the first report of a fusion transcript in osteosarcoma that demonstrates the relation of molecular mechanism of SCOS subtype to that of Ewing sarcoma. The 3'end fusion partner and the inferred structure of the new EWSR1-CREB3L1 chimera, however, are different from those underlying Ewing sarcoma, predicting different functions of the novel fusion product. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 253.