title: A complex genetic rearrangement in a t(10;14)(q24;q11) associated with T-cell acute lymphoblastic leukemia.
abstract: The t(10;14)(q24;q11) is observed in the leukemia cells of 5-10% of cases of T-cell acute lymphoblastic leukemia (T-ALL). Recently, molecular analyses of a number of these translocations revealed simple reciprocal translocations between the T-cell receptor delta chain gene (TCRD) and a region of 10q24. We have characterized, at the molecular level, a t(10;14)(q24;q11) in a patient with T-ALL. The translocation in this case, in contrast to the previous cases, is part of a complex genetic rearrangement. In addition to a reciprocal translocation between the D delta 3 gene segment of TCRD and a region of 10q24, a local inversion occurred within TCRD, involving the D delta 2 and V delta 2 gene segments. As a consequence, the entire joining and constant regions and most of the diversity regions of TCRD are located on the derivative 14 chromosome, whereas the joining and constant regions of TCRA are positioned on the derivative 10 chromosome. The chromosome 10 breakpoint in our patient, as in other t(10;14), clusters within a 9 kb breakpoint region. The occurrence of seven breakpoints within a localized region of chromosome 10 implies the existence of a nearby gene whose activation may have conferred a selective advantage on the leukemia cells. Moreover, as in the previous cases, the translocation in the present study exhibits recombination signal sequences or signal-like sequences adjacent to the breakpoint junction. The presence of such motifs suggests the involvement of the recombinase enzyme system in the generation of this genetic alteration.
authors.affiliation: Department of Medicine, University of Chicago, Illinois 60637.
authors.forename: J K
authors.initials: JK
authors.lastname: Park
authors.forename: M M
authors.initials: MM
authors.lastname: Le Beau
authors.forename: T B
authors.initials: TB
authors.lastname: Shows
authors.forename: J D
authors.initials: JD
authors.lastname: Rowley
authors.forename: M O
authors.initials: MO
authors.lastname: Diaz
mesh_terms: D001483:Base Sequence; D002648:Child; D002879:Chromosomes, Human, Pair 10 / Q000648:ultrastructure*; D002883:Chromosomes, Human, Pair 14 / Q000648:ultrastructure*; D004254:DNA Nucleotidyltransferases / Q000502:physiology; D004273:DNA, Neoplasm / Q000235:genetics; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D005796:Genes; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D015345:Oligonucleotide Probes; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D014178:Translocation, Genetic; D045567:VDJ Recombinases
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D015345:Oligonucleotide Probes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases