Miho Kawamura-Saito, Yukari Yamazaki, Keiko Kaneko, Noriyoshi Kawaguchi, Hiroaki Kanda, Hiroyuki Mukai, Takahiro Gotoh, Tohru Motoi, Masashi Fukayama, Hiroyuki Aburatani, Toichiro Takizawa, Takuro Nakamura
Ewing's family tumors (EFTs) are highly malignant tumors arising from bone and soft tissues that exhibit EWS-FLI1 or variant EWS-ETS gene fusions in more than 85% of the cases. Here we show that CIC, a human homolog of Drosophila capicua which encodes a high mobility group box transcription factor, is fused to a double homeodomain gene DUX4 as a result of a recurrent chromosomal translocation t(4;19)(q35;q13). This translocation was seen in two cases of soft tissue sarcoma diagnosed as Ewing-like sarcoma. CIC-DUX4 exhibits a transforming potential for NIH 3T3 fibroblasts, and as a consequence of fusion with a C-terminal fragment of DUX4, CIC acquires an enhanced transcriptional activity, suggesting that expression of its downstream targets might be deregulated...
July 1, 2006: Human Molecular Genetics