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A complex genetic rearrangement in a t(10;14)(q24;q11) associated with T‐cell acute lymphoblastic leukemia
Author(s) -
Park James K.,
Le Beau Michelle M.,
Rowley Janet D.,
Diaz Manuel O.,
Shows Thomas B.
Publication year - 1992
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.2870040105
Subject(s) - chromosomal translocation , breakpoint , biology , gene , chromosome , derivative chromosome , genetics , lymphoblastic leukemia , recombinase , microbiology and biotechnology , gene rearrangement , chromosomal inversion , recombination , leukemia , karyotype , chromosome 22
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 Dδ3 gene segment of TCRD and a region of 10q24, a local inversion occurred within TCRD , involving the Dδ2 and Vδ2 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.