Alternative titles; symbols
HGNC Approved Gene Symbol: TCL6
Cytogenetic location: 14q32.13 Genomic coordinates (GRCh38): 14:95,652,097-95,673,452 (from NCBI)
In the course of characterizing the TML1 gene (TCL1B; 603769), which resides along with TCL1 (TCL1A; 186960) in the chromosome 14q32.1 region commonly involved in chromosomal rearrangements with T-cell receptor (TCR) loci (see 186880) in several neoplasms, Saitou et al. (2000) identified a third gene, TCL6 (T-cell leukemia/lymphoma-6), within the breakpoint cluster region. The TCL6 gene expresses at least 11 isoforms through complex alternative splicing, including splicing with the TML1 gene. Those isoforms encode at least 5 open reading frames. Saitou et al. (2000) investigated the subcellular localization of these open reading frames by tagging them with green fluorescent protein (GFP) at their C termini and expressing them in COS-7 cells. Two of the open reading frames were localized to the cytoplasm, while the other 3 were nuclear. Northern blot analysis revealed 3 transcripts in kidney (5.0, 4.0, and 3.2 kb) and 3 transcripts in placenta (5.5, 4.5, and 4.0 kb). RT-PCR assays revealed strong expression of TCL6 in placenta and kidney, and low expression in tonsil, spleen, and lymph node. Among tumor cells, high expression was observed in acute T-cell leukemia, Burkitt lymphoma (113970), B lymphocytic leukemia (109543), and Hodgkin disease (236000) cell lines. Saitou et al. (2000) concluded that the TCL6 gene and TCL6-TML1 fusion transcripts are expressed mainly in the B cell lineage and are not expressed in T cells; like the TCL1 and TML1 genes, they become deregulated as a consequence of their juxtaposition to the TCR-alpha (see 186880)/TCR-delta (see 186810) locus.
In a note added in proof, Saitou et al. (2000) stated that the TNG1 and TNG2 genes identified by Hallas et al. (1999) are isoforms of the TCL6 gene and correspond to transcripts designated A1 and A3, respectively. Hallas et al. (1999) had found that TNG1 and TNG2 encode proteins of 141 and 110 amino acids, respectively. TNG1 and TNG2 expression was detected by RT-PCR at low levels in a wide variety of normal tissues. Adult human thymus expressed only TNG2, while fetal thymus showed only TNG1 expression. TNG1 and TNG2 also were activated in T-cell leukemias with rearrangements at 14q32.1.
Saitou et al. (2000) determined that the TCL6 gene has at least 12 exons with small alternative exons.
Saitou et al. (2000) mapped the TCL6 gene 7 kb centromeric to the TML1 gene on chromosome 14q32. TCL6 is transcribed in the same direction as TML1.
Hallas, C., Pekarsky, Y., Itoyama, T., Varnum, J., Bichi, R., Rothstein, J. L., Croce, C. M. Genomic analysis of human and mouse TCL1 loci reveals a complex of tightly clustered genes. Proc. Nat. Acad. Sci. 96: 14418-14423, 1999. [PubMed: 10588720] [Full Text: https://doi.org/10.1073/pnas.96.25.14418]
Saitou, M., Sugimoto, J., Hatakeyama, T., Russo, G., Isobe, M. Identification of the TCL6 genes within the breakpoint cluster region on chromosome 14q32 in T-cell leukemia. Oncogene 19: 2796-2802, 2000. [PubMed: 10851082] [Full Text: https://doi.org/10.1038/sj.onc.1203604]