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Other entities represented in this entry:
HGNC Approved Gene Symbol: TAF15
Cytogenetic location: 17q12 Genomic coordinates (GRCh38) : 17:35,809,484-35,847,242 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 17q12 | Chondrosarcoma, extraskeletal myxoid | 612237 | 1 |
The EWS gene (EWSR1; 133450) was found at the chromosome breakpoints in Ewing sarcoma (612219) and maps to chromosome 22; the FUS/TLS gene (137070) was found at the breakpoints of myxoid liposarcoma and acute myeloid leukemia and maps to chromosome 16. These genes encode proteins that carry a highly homologous RNA binding domain. Fusion proteins made between the N-terminal half of either gene and transcriptional regulatory proteins, also derived from genes located at breakpoints, appear to be involved in the pathogenesis of tumors. By PCR amplification of human Namalwa cell cDNA using degenerate primers made from the conserved amino acid sequences in the RNA binding domain of EWS and FUS/TLS, Morohoshi et al. (1996) obtained a cDNA fragment, designated RBP56. This fragment was predicted to encode an amino acid sequence similar but not identical to those of EWS and FUS/TLS. Using this fragment as a probe, they obtained 2 isoforms of cDNAs consisting of 2,144 and 2,153 bp, respectively, which encoded proteins consisting of 589 and 592 amino acid residues, respectively. The expression of RBP56 mRNA was observed in all human fetal and adult tissues examined, as was the expression of EWS and FUS/TLS mRNAs.
By genomic sequence analysis, Morohoshi et al. (1998) determined that the RBP56 gene spans about 37 kb and contains 16 exons ranging in size from 33 bp to 562 bp. The longest, exon 15, encodes a C-terminal region with 19 repeats. The authors noted that the conservation of the overall exon number and structure of RBP56, FUS/TLS, and EWS indicates that they probably originated from the same ancestor gene.
Morohoshi et al. (1996) mapped the TAF15 (RBP56) gene to chromosome 17 by Southern blot analysis of mouse/human somatic cell hybrids and localized it to 17q11.2-q12 by FISH. By PCR analysis using genomic DNA from human/rodent somatic cell hybrid panels harboring part of human chromosome 17, they further localized the gene to 17q11.1-q11.2.
RBP56/NR4A3 Fusion Gene
Although most extraskeletal myxoid chondrosarcomas (EMC; 612237) are characterized by the translocation t(9;22)(q22;q12), another subset carries a t(9;17)(q22;q11). The t(9;22) is known to result in fusion of the EWS gene on 22q12 with the NR4A3 gene (600542) on 9q11, creating a chimeric EWS/NR4A3 gene. Panagopoulos et al. (1999) examined 2 extraskeletal myxoid chondrosarcomas with t(9;17)(q22;q11) and found that the NR4A3 gene, which they designated CHN, was combined with the RBP56 gene from 17q11 to generate a chimeric RBP56/NR4A3 gene. RBP56 had not previously been implicated in tumorigenesis, but it encodes a putative RNA-binding protein similar to the EWS and FUS genes known to play a pathogenetic role in sarcomas. The presence of the RBP56/NR4A3 chimeric gene in extraskeletal myxoid chondrosarcomas showed that the N-terminal parts of EWS and RBP56 have similar oncogenic potential, making them pathogenetically equivalent in oncoproteins arising from fusions with certain transcription factors.
Morohoshi, F., Arai, K., Takahashi, E., Tanigami, A., Ohki, M. Cloning and mapping of a human RBP56 gene encoding a putative RNA binding protein similar to FUS/TLS and EWS proteins. Genomics 38: 51-57, 1996. [PubMed: 8954779] [Full Text: https://doi.org/10.1006/geno.1996.0591]
Morohoshi, F., Ootsuka, Y., Arai, K., Ichikawa, H., Mitani, S., Munakata, N., Ohki, M. Genomic structure of the human RBP56/hTAF(II)68 and FUS/TLS genes. Gene 221: 191-198, 1998. [PubMed: 9795213] [Full Text: https://doi.org/10.1016/s0378-1119(98)00463-6]
Panagopoulos, I., Mencinger, M., Dietrich, C. U., Bjerkehagan, B., Saeter, G., Mertens, F., Mandahl, N., Heim, S. Fusion of the RBP56 and CHN genes in extraskeletal myxoid chondrosarcomas with translocation t(9;17)(q22;q11). Oncogene 18: 7594-7598, 1999. [PubMed: 10602519] [Full Text: https://doi.org/10.1038/sj.onc.1203155]