c-tal, a helix-loop-helix protein, is juxtaposed to the T-cell receptor-beta chain gene by a reciprocal chromosomal translocation: t(1;7)(p32;q35).
Studies on nonrandom chromosomal translocations have been important for the identification of genes potentially involved in the malignant transformation of cells. The most widely studied translocations, involving members of the Ig supergene family, have shown juxtapositions of proto-oncogenes with the rearranging loci. Such translocations can inappropriately activate expression of the proto-oncogenes and thereby play a role in tumorigenesis. Because the cytogenetic analysis of a bone marrow sample from a child with T-cell acute lymphoblastic leukemia showed a (1;7)(p32;q35) translocation, we sought to determine if the translocation breakpoint was in the T-cell receptor (TCR)-beta gene locus on chromosome 7. Analysis of the TCR-beta gene by Southern blotting showed three rearranged bands. Nucleotide sequencing and Southern blot analysis of TCR-beta genomic clones, isolated from patient DNA, showed that one contained a normal rearrangement of the TCR-beta gene using V beta 12.2, D beta 2.1, and J beta 2.5, whereas two other clones contained DNA from derivative chromosomes 1 and 7. Chromosomal mapping showed that the (1;7) translocation breakpoint was 35 kb 3' to the c-tal gene locus. The juxtaposition of c-tal to the TCR-beta locus may enhance c-tal expression and contribute to T-cell leukemogenesis.
Fitzgerald
T J
TJ
Department of Virology and Molecular Biology, St Jude Children's Research Hospital, Memphis, TN 38101.
Neale
G A
GA
Raimondi
S C
SC
Goorha
R M
RM
D000293:Adolescent; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D015139:Blotting, Southern; D002878:Chromosomes, Human, Pair 1; D002897:Chromosomes, Human, Pair 7; D002999:Clone Cells; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000235:genetics*; D015698:Genomic Library; D006801:Humans; D016130:Immunophenotyping; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D015183:Restriction Mapping; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D014178:Translocation, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D015342:DNA Probes; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C067143:TAL1 protein, human