Identification and Characterization of Novel Candidate Oncogenes

Abstract: Using computer-assisted sequence homology searches we identified three genes encoding proteins similar to certain fusion partner proteins in cancer. The novel APRIL gene was localized to 15q25 and encodes a protein, containing an acidic amino-acid region similar to that/those of leukemia-associated fusion partner proteins DEK and SET. The N-terminus of APRIL contains leucine-rich repeats. The mouse APRIL cDNA sequence is also described. Human APRIL is present in the nucleoplasm.The APRIL is expressed in majority of human adult and mouse embryonic cell types. Furthermore, it seems to be overexpressed in astrocytomas. The novel TFG gene maps to 3q11-12. The protein contains a coiled-coil domain and shares a region rich in S, P, Y, G, and Q amino acids with sarcoma-asociated FUS and EWS. Mouse and C. elegans TFG orthologus, as well as the N-terminal part of TFG from pig, zebra fish and S. mansoni, were also identified. The TFG gene is expressed in a wide range of human adult and mouse embryonic tissues. The TFG protein localizes to unknown cytoplasmic structures. However, a diffuse nuclear fluorescence was observed upon deletion of the TFG coiled-coil domain. The 5' end of TFG cDNA corresponds to the sequence previously reported to be fused to the 3' end of the NTRK1 in papillary thyroid carcinoma. The recently descibed RBP56 protein is highly homologous to EWS and FUS. We have found that a subset of extraskeletal myxoid chondrosarcomas contain a fusion gene between the RBP56 gene on 17q11 and the CHN gene on 9q22, encoding RBP56-CHN fusion protein.