The mechanism of chromosome 14 inversion in a human T cell lymphoma.
The chromosome 14 inversion produces cytogenetic breakpoints at either end of the long arm of this chromosome. Previous studies have shown that a hybrid gene (designated IgT) consisting of an immunoglobulin VH gene segment and T cell receptor J alpha C alpha segments encompasses the telomeric breakpoint in SUP-T1, a cell line derived from a human T cell lymphoma. Here, we report that the centromeric breakpoint in SUP-T1 constitutes the reciprocal of a VH-J alpha join but involves gene segments different from those at the telomeric breakpoint. Therefore, chromosome inversion and IgT formation were mediated by two sequential VH-J alpha joining events. Moreover, sequences adjacent to the centromeric breakpoint detect a T-cell-specific RNA, encoded within the immunoglobulin VH locus, whose transcriptional activity may have facilitated the illegitimate VH-J alpha rearrangements.
D007446:Chromosome Inversion; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D004262:DNA Restriction Enzymes / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008223:Lymphoma / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000502:physiology
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004262:DNA Restriction Enzymes