Growth of large chromosomally abnormal T cell clones in ataxia telangiectasia patients is associated with translocation at 14q11. A model for other T cell neoplasia.
Human T cell malignancies often show chromosome breaks at 14q11, within the alpha chain locus of the human T cell antigen receptor, with translocation of the distal portion of 14 to one of several sites. In patients with ataxia telangiectasia (A-T) the majority of T cell chromosome translocations associated with this disorder appear to occur at the sites of the T cell antigen receptor genes 7p14, 7q35, and 14q11 and may result in clone formation. In three large proliferating A-T T cell clones we have observed (including one which became malignant) and in most T cell tumours reported, the clonal chromosome exchange involves one breakpoint at 14q11 with the second breakpoint occurring in a gene not involved in the immunoglobulin supergene family. Our observations on A-T patients confirm the suggestion that chromosome exchanges involving either t(7;14)(p14;q11), t(7;14)(q35;q11), inv(7)(p14q35), or t(7;7)(p14;q35) confer only a small proliferative advantage on T cells in vivo without the capacity for malignant transformation and that the potential for malignant change is not a feature of all these rearrangements, but is restricted to cells or clones with other chromosome exchanges.
D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000276:immunology; D002471:Cell Transformation, Neoplastic; D002871:Chromosome Banding; D002883:Chromosomes, Human, Pair 14; D002999:Clone Cells; D006801:Humans; D007621:Karyotyping; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014178:Translocation, Genetic; D014960:X Chromosome
D011948:Receptors, Antigen, T-Cell