Abstract 4197: Discovering FUS-CHOP targets: A Chip-Seq approach

Abstract

Abstract Myxoid liposarcoma (M-LS) is one of the most common soft tissue sarcomas in adults. Approximately 90% of cases show the characteristic t(12;16)(q13;p11) translocation, which produces the FUS-CHOP (FC) oncogene. FUS is a RNA-binding protein expressed in several tissues; CHOP a bZIP transcription factor involved in adipocyte differentiation. Although it is known that CHOP bZIP region is essential for FC-induced transformation, little is known about FC transcriptional targets and how FC participates in the development and progression of M-LS. Moreover, it is unclear whether FC controls the transcription of a set of genes different from the set controlled by CHOP. Understanding how the FUS-CHOP fusion protein causes M-LS will aid in the development of novel targeted therapies. To shed light on this issue we sought to exploit the ChIP-Seq technique (Chromatin Immunoprecipitation followed by next generation sequencing). To this end, chromatin immunorecipitation was performed on cell lines expressing FC (endogenous or ectopic). DNA co-precipitated together with the FC protein was analyzed by using an Illumina GAIIX platform. FC-bound DNA was mapped to the genome using the aligner Bowtie and the enriched regions were identified by using the MACS peak caller. ChIP-Seq data were combined with RNA-seq analysis to screen for the potential targets. Our approach was validated by the identification of LONP1, CLCN3 and GADD34, which have been previously reported to be modulated by CHOP. The most interesting candidates will be further investigated for their implication in FC development and progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4197. doi:1538-7445.AM2012-4197