Abstract
Chromosomal translocations in T-cell malignancies frequently involve the T-cell receptor (TCR)α/δ locus at chromosome 14q11. Although 14q11 abnormalities are found in about 10% of adult T-cell leukemia (ATL) cases, until now there has been no direct evidence showing involvement of the TCR locus in ATL—a malignancy closely associated with HTLV-1 infection. The breakpoints of T-cell malignancies most commonly occur within the Jα or Jδ region of the TCR locus. In ATL, however, despite extensive searching no breakpoint has yet been found in that region. Using fluorescence in situ hybridization with a panel of cosmid and bacterial artificial chromosome probes derived from chromosome 14, including the variable region of the TCRα locus, comprehensive analysis of an ATL patient carrying inv(14)(q11q32) revealed that the TCR locus was indeed involved in this inversion. Molecular cloning of the breakpoint revealed the juxtaposition of TCR Vα to the 14q24 region as a result of two consecutive inversions: inv(14)(q11q32) and inv(14)(q11q24). We also found a gene near the breakpoint at the 14q24 region that is downregulated in this ATL patient and is assigned in the database as a pseudogene of ADAM21 (a disintegrin and metalloproteinase domain 21). Our expression analysis, however, showed that this pseudogene was actually expressed and was capable of encoding a protein similar to ADAM21; thus we have named this gene ADAM21-like (ADAM21-L).
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Acknowledgements
This research was partially supported by a grant-in-aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan. We would like to thank Dr. Masumichi Saitou for providing us with the cosmid clones specific to Vα locus.
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The ADAM21-L gene and breakpoint sequences have been deposited with the GenBank database under accession numbers DQ202398 and DQ302756, respectively.
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Haider, S., Hayakawa, K., Itoyama, T. et al. TCR variable gene involvement in chromosome inversion between 14q11 and 14q24 in adult T-cell leukemia. J Hum Genet 51, 326–334 (2006). https://doi.org/10.1007/s10038-006-0364-y
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DOI: https://doi.org/10.1007/s10038-006-0364-y
