This report describes cancer, sarcoma, CIC-DUX4 fusion (CDS); the cancers associated with this translocation are also described as Ewing-like sarcomas and round cell sarcomas. The two human genes involved in this translocation both play roles in regulation of transcription: CIC, which encodes an HMG-box-containing transcriptional repressor, and DUX4, which encodes a homeobox-containing protein that acts primarily as transcriptional activator. CIC-DUX4 translocations are found in sarcomas from various different types of soft tissue.
A Drosophila model makes use of a fusion construct with the CIC 5' sequences contributed by the orthologous Drosophila gene, cic, fused to 3' sequences of the human Hsap\DUX4 gene. The functions of the HMG-box and C1 domains of the cic portion of the fusion gene have been characterized in this system, defining the the key role of C1 in DNA binding. It is observed that this domain is intact in oncogenic CIC-DUX4 fusions.
[updated Feb. 2020 by FlyBase; FBrf0222196]
CIC-DUX4 fusion-positive sarcomas are aggressive tumours with an adverse prognosis, and with clinical, histological and genetic differences from Ewing sarcoma. CDSs mostly arising in deep or superficial soft tissue, or, very rarely, in viscera. (Gambarotti et al., 2016; pubmed:27079694).
A copy of DUX4 is found within each of up to 100 copies of the D4Z4 macrosatellite repeat in the subtelomeric region of chromosome 4q. Only the last repeat appears to encode a functional DUX4 transcript with a polyadenylation site that lies telomeric and outside the D4Z4 repeat region (summary by Snider et al., 2010; pubmed:21060811). [from MIM:606009; 2020.02.29]
A tandem homeodomain architecture within a single protein is highly unusual: there are no double homeodomain proteins in species outside of placental mammals (Lee et al., 2018; pubmed:30540931).
DUX4, named 'double homeobox 4', encodes a protein involved in transcriptional regulation of numerous genes, primarily as transcriptional activator, but also mediates repression of a set of target genes. [Gene Cards, DUX4; 2020.02.29]
CIC encodes an ortholog of the Drosophila melanogaster capicua gene, is a member of the high mobility group (HMG)-box superfamily of transcriptional repressors, and is involved in the development of the central nervous system. [Gene Cards, CIC; 2020.02.29]
DUX4 encodes a putative transcription factor that contains 2 homeobox domains. [from MIM:606009; 2020.02.29]
Although multiple paired homeobox transcription factors share some homology, there are no moderate- or high-scoring orthologs of DUX4 in Drosophila.
One to one: 1 human to 1 Drosophila.
