Translin binds to the sequences adjacent to the breakpoints of the TLS and CHOP genes in liposarcomas with translocation t(12;16)

• Published in: Oncogene Vol. 19; no. 50; pp. 5821 - 5825
• Main Authors: HOSAKA, Taisuke, KANOE, Hiroshi, NAKAMURA, Takashi, TOGUCHIDA, Junya, NAKAYAMA, Tomitaka, MURAKAMI, Hiroshi, YAMAMOTO, Hiroshi, NAKAMATA, Takeharu, TSUBOYAMA, Tadao, OKA, Masanori, KASAI, Masataka, SASAKI, Masao S
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 23-11-2000; Nature Publishing Group
• Subjects: Binding Sites; Biological and medical sciences; Bone surgery; Breakpoints; CCAAT-Enhancer-Binding Proteins - genetics; Cell interactions, adhesion; CHOP gene; chromosome 12; chromosome 16; Chromosome Breakage; Chromosome translocations; Chromosomes; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 16; Consensus Sequence; DNA binding proteins; DNA, Neoplasm - genetics; DNA, Neoplasm - metabolism; DNA-Binding Proteins - metabolism; Electrophoretic mobility; fibrosarcoma; Fundamental and applied biological sciences. Psychology; Fusion protein; Genes; Genetic aspects; HeLa Cells; Humans; Leukemia; liposarcoma; Liposarcoma, Myxoid - genetics; Liposarcoma, Myxoid - metabolism; Molecular and cellular biology; Oligonucleotides; Oligonucleotides - genetics; Oligonucleotides - metabolism; Oncogene Proteins, Fusion - genetics; Orthopedics; Physiological aspects; Proteins; Risk factors; RNA-Binding Protein FUS; Sarcoma; Substrate Specificity; TLS gene; Transcription Factor CHOP; translin; Translocation (Genetics); Translocation, Genetic; TSN protein; Tumors; Japan; Human; Binding; Translocation; Nucleotide sequence; Chromosome; Homology; Protein; Binding protein; Cell line; Shutdown; Gene; Liposarcoma; Oligonucleotide
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1203943

Myxoid and round-cell liposarcomas share the translocation t(12;16)(q13;p11) creating the TLS-CHOP fusion gene as a common genetic alteration. We previously reported several unique characteristics of genomic sequences around the breakpoints in the TLS and CHOP loci, and among them was the presence of consensus recognition motifs of Translin, a protein that associates with chromosomal translocations of lymphoid neoplasms. We further extended our search for Translin binding motifs in sequences adjacent to breakpoints and investigated whether Translin binds to these sequences in vitro by mobility-shift assay. Computer-assisted search found sequences highly homologous (>70%) with Translin binding motifs adjacent to the breakpoints in 10 out of 11 liposarcomas with the TLS-CHOP fusion genes. All of 13 oligonucleotides corresponding to the putative binding sequences in these cases bind to Hela cell extract and also recombinant Translin protein, although the binding affinity of each motif showed considerable differences. The DNA-protein complex formation was inhibited by non-labeled competitor or anti-Translin antibody, suggesting the specificity of the complex formation. Considering the high incidence and specific binding property, the presence of Translin binding motif may be one of the important determinants for the location of breakpoints in the TLS and CHOP genes in liposarcomas.