TCR variable gene involvement in chromosome inversion between 14q11 and 14q24 in adult T-cell leukemia.
Chromosomal translocations in T-cell malignancies frequently involve the T-cell receptor (TCR)alpha/delta 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 Jalpha or Jdelta 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 TCRalpha 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 Valpha 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).
Haider
Shawkat
S
Laboratory of Molecular and Cellular Biology, Department of Materials and Biosystem Engineering, Faculty of Engineering, Toyama University, 3190 Gofuku, Toyama, 930-8555, Japan.
Hayakawa
Kousuke
K
Laboratory of Molecular and Cellular Biology, Department of Materials and Biosystem Engineering, Faculty of Engineering, Toyama University, 3190 Gofuku, Toyama, 930-8555, Japan.
Itoyama
Takahiro
T
Laboratory of Molecular and Cellular Biology, Department of Materials and Biosystem Engineering, Faculty of Engineering, Toyama University, 3190 Gofuku, Toyama, 930-8555, Japan.
Sadamori
Naoki
N
Department of Nursing, Siebold University of Nagasaki, Nagasaki, 851-2195, Japan.
Kurosawa
Nobuyuki
N
Laboratory of Molecular and Cellular Biology, Department of Materials and Biosystem Engineering, Faculty of Engineering, Toyama University, 3190 Gofuku, Toyama, 930-8555, Japan.
Isobe
Masaharu
M
Laboratory of Molecular and Cellular Biology, Department of Materials and Biosystem Engineering, Faculty of Engineering, Toyama University, 3190 Gofuku, Toyama, 930-8555, Japan. isobe@eng.toyama-u.ac.jp.
D051722:ADAM Proteins / Q000378:metabolism; D000072199:ADAM12 Protein; D000328:Adult; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D007446:Chromosome Inversion; D002883:Chromosomes, Human, Pair 14; D004247:DNA / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D015973:Gene Expression Regulation, Leukemic; D019672:Genes, T-Cell Receptor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008565:Membrane Proteins / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014162:Transfection
D008565:Membrane Proteins; D004247:DNA; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human