Identification of an aberrant type of rearrangement in the T-cell receptor alpha/delta locus in adult T-cell leukemia.
V(D)J recombination is the mechanism by which antigen receptor genes are assembled by three basic steps: cleavage, processing of broken DNA ends, and joining. In this process of recombination, the broken DNA molecules excised from different receptor gene loci are often joined to generate interlocus joints. The interlocus recombination process contributes to the translocation between antigen receptor genes and oncogenes, leading to the malignant transformation of lymphocytes. The alpha and delta chain of the T-cell receptor (TCR alpha/delta) locus at chromosome 14q11 is also a region where several types of chromosome translocations occur in T-cell malignancies. In the process of analyzing TCR alpha rearrangements in a patient with adult T-cell leukemia (ATL) carrying a translocation at chromosome 14q11, we found novel complex rearrangements in the Jalpha locus. On the one hand, the V2.3 gene is joined to the heptamernonamer recombination signal sequence of the J37 gene, and, on the other hand, the J37 gene is joined to the V2.3 recombination signal sequence through head-to-head fusion. These recombination products or hybrid joints originated through an inversion of about 70kb DNA. Interestingly, the inverted DNA stretch contains a normal V8.1-J40 rearrangement. These findings are the first direct demonstration that successive rearrangements with hybrid joints occur on the same chromosome in the human TCR alpha locus.
Saitou
M
M
Department of Materials and Biosystem Engineering, Faculty of Engineering, Toyama University, Japan.
Sadamori
N
N
Isobe
M
M
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D004273:DNA, Neoplasm / Q000235:genetics; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D006801:Humans; D007621:Karyotyping; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000276:immunology*; D008969:Molecular Sequence Data; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D004273:DNA, Neoplasm