Molecular Analysis of a t(14;14) Translocation in Leukemic T-Cells of an Ataxia Telangiectasia Patient

We have detected and cloned two rearrangements in the T-cell receptor α locus from a clone of somatic cell hybrids carrying a t(14;14)(q11;q32) chromosomal translocation derived from an ataxia telangiectasia patient with T-cell chronic lymphocytic leukemia. The T-cell clone carrying the t(14;14) chromosomal translocation was known to be present for > 10 years before the onset of overt leukemia. One molecular rearrangement of the T-cell receptor α locus corresponded to a functional variable-joining region (V-J) joining, whereas the other derived from the breakpoint of the t(14;14)(q11;q32) translocation. Chromosomal in situ hybridization of the probe derived from the t(14;14) breakpoint localized the breakpoint region to 14q32.1, apparently the same region that is involved in another ataxia telangiectasia characteristic chromosome translocation, t(7;14)(q35;q32). The 14q32.1 breakpoint is at least 10,000 kilobase pairs (kbp) centromeric to the immunoglobulin heavy chain locus. Sequence analysis of the breakpoint indicates the involvement of a Jα sequence during the translocation. Comigration of high-molecular weight DNA fragments involved with t(7;14) and t(14;14) translocations suggests the presence of a cluster of breakpoints in the 14q32.1 region, the site of a putative oncogene, TCL1.