title: A chromosome 14 inversion in a T-cell lymphoma is caused by site-specific recombination between immunoglobulin and T-cell receptor loci.
abstract: Specific chromosomal aberrations are associated with specific types of cancer (for review see ref. 1). The distinctiveness of each association has led to the belief that these chromosomal aberrations are clues to oncogenic events or to the state of differentiation in the malignant cell type. Malignancies of T lymphocytes demonstrate such an association characterized most frequently by structural translocations or inversions of chromosomes 7 and 14 (refs 7-9). Analyses of these chromosomally marked tumours at the molecular level may therefore provide insight into the aetiology of the cancers as well as the mechanisms by which chromosomes break and rejoin. Here we report such an analysis of the tumour cell line SUP-T1 derived from a patient with childhood T-cell lymphoma carrying an inversion of one chromosome 14 between bands q11.2 and q32.3, that is, inv(14) (q11.2; q32.2). These are the same chromosomal bands to which the T-cell receptor alpha-chain (14q11.2) and the immunoglobulin heavy-chain locus (14q32.3) have been assigned. Our analysis reveals that this morphological inversion of chromosome 14 was mediated by a site-specific recombination event between an immunoglobulin heavy-chain variable region (Ig VH) and a T-cell receptor (TCR) alpha-chain joining segment (TCR J alpha). S1 nuclease analysis shows that this hybrid gene is transcribed into poly(A)+ RNA.
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D007446:Chromosome Inversion; D002874:Chromosome Mapping; D002901:Chromosomes, Human, 13-15; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D006801:Humans; D008223:Lymphoma / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011971:Receptors, Immunologic / Q000235:genetics*; D011995:Recombination, Genetic; D015719:Single-Strand Specific DNA and RNA Endonucleases; D013601:T-Lymphocytes
chemical_list: D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D004720:Endonucleases; D004262:DNA Restriction Enzymes; D015719:Single-Strand Specific DNA and RNA Endonucleases