HGNC Approved Gene Symbol: TAL2
Cytogenetic location: 9q31.2 Genomic coordinates (GRCh38): 9:105,662,457-105,663,124 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 9q31.2 | Leukemia, T-cell acute lymphocytic, somatic | 613065 | 3 |
Tumor-specific alteration of the TAL1 gene (187040) occurs in almost 25% of patients with T-cell acute lymphoblastic leukemia (T-ALL). The TAL1 gene product is a helix-loop-helix (HLH) protein which shares 87% amino acid sequence identity with LYL1 (151440), another HLH protein involved in T-cell leukemogenesis. Xia et al. (1991) identified a distinct gene, called TAL2, on the basis of its sequence homology with TAL1. They demonstrated that TAL2 is located 33 kb from the chromosome 9 breakpoint of t(7;9)(q34;q32), a recurring translocation specifically associated with T-ALL. The translocation juxtaposes TAL2 with sequences from the T-cell receptor beta-chain gene (TCRB; see 186930) on chromosome 7. The TAL2 gene product includes an HLH protein dimerization domain and a DNA-binding domain that are homologous to those encoded by the TAL1 and LYL1 protooncogenes. Tycko et al. (1989) had characterized t(7;9) at the molecular level in 3 patients with T-ALL and found that the chromosome 9 breakpoints were tightly clustered within a 31-bp sequence. Xia et al. (1991) demonstrated direct linkage between TAL2 and the t(7;9) breakpoint region by chromosome walking.
TAL2 is 1 of at least 9 different protooncogenes that are activated as a consequence of translocation to 1 of the T-cell receptor loci in T-ALL. Molecular and functional analysis of the breakpoints suggested a unifying mechanistic model in which the translocation results from a mistake occurring during V(D)J recombination. In most cases, oncogene activation is a direct result of the juxtaposition of the protooncogene and T-cell receptor regulatory elements on one of the derivative chromosomes. Thus, chromosomal translocations are generally assumed to be the initiating leukemogenic events and constitute important diagnostic markers of neoplasia. The t(7;9)(q34;q32) translocation is believed to be representative of this paradigm. The translocation is mediated by V(D)J recombination using a fortuitous recombination site located 3-prime of the TAL2 protooncogene, and the consequent juxtaposition of TAL2 and the TCR-beta enhancer on the der(9) chromosome results in TAL2 overexpression. A direct leukemogenic role of TAL2 is supported by its structural and functional relationship to the protooncogenes TAL1 and LYL1, which are similarly activated in individuals with T-ALL and encode a specific class of bHLH proteins with oncogenic features. To further define the role of TAL2 translocation in the development of T-ALL, Marculescu et al. (2003) investigated the occurrence of t(7;9)(q34;q32) in healthy individuals. PCR analysis of thymus samples from 10 otherwise normal children undergoing thoracic surgery revealed the presence of this translocation in 6 of 10 samples at an estimated frequency of roughly 1 in 10 million thymic cells. They then cloned and sequenced the PCR products. Notably, they found that the der(9) breakpoints were distinct between individuals with T-ALL and healthy individuals. In leukemic individuals, a fusion between the fortuitous recombination site 3-prime of TAL2 and the J-beta-2 coding segment was invariably observed. In contrast, breakpoints from healthy individuals contained a fusion between the TAL2 recombination site and the D-beta-1 recombination signal sequence in a signal-joint configuration. The observation indicated that signal joints constitute unstable genomic elements with potential oncogenic properties.
Xia et al. (1991) performed the chromosomal localization of TAL2 to chromosome 9 by using a genomic DNA fragment as a probe in Southern hybridization with DNAs from a panel of human/hamster somatic cell hybrids. The regional localization to 9q31 was determined by fluorescence in situ hybridization.
By interspecific backcross linkage analysis, Pilz et al. (1995) mapped the Tal2 gene to mouse chromosome 4.
Marculescu, R., Vanura, K., Le, T., Simon, P., Jager, U., Nadel, B. Distinct t(7;9)(q34;q32) breakpoints in healthy individuals and individuals with T-ALL. Nature Genet. 33: 342-344, 2003. [PubMed: 12567187] [Full Text: https://doi.org/10.1038/ng1092]
Pilz, A., Woodward, K., Povey, S., Abbott, C. Comparative mapping of 50 human chromosome 9 loci in the laboratory mouse. Genomics 25: 139-149, 1995. [PubMed: 7774911] [Full Text: https://doi.org/10.1016/0888-7543(95)80119-7]
Tycko, B., Reynolds, T. C., Smith, S. D., Sklar, J. Consistent breakage between consensus recombinase heptamers of chromosome 9 DNA in a recurrent chromosomal translocation of human T cell leukemia. J. Exp. Med. 169: 369-377, 1989. [PubMed: 2536065] [Full Text: https://doi.org/10.1084/jem.169.2.369]
Xia, Y., Brown, L., Yang, C. Y.-C., Tsou Tsan, J., Siciliano, M. J., Espinosa, R., III, Le Beau, M. M., Baer, R. J. TAL2, a helix-loop-helix gene activated by the (7;9)(q34;q32) translocation in human T-cell leukemia. Proc. Nat. Acad. Sci. 88: 11416-11420, 1991. [PubMed: 1763056] [Full Text: https://doi.org/10.1073/pnas.88.24.11416]