Molecular analysis of a t(14;14) translocation in leukemic T-cells of an ataxia telangiectasia patient.
We have detected and cloned two rearrangements in the T-cell receptor alpha locus from a clone of somatic cell hybrids carrying a t(14;14)(q11;q32) chromosomal translocation derived from an ataxia telangiectasia patient with T-cell chronic lymphocytic leukemia. The T-cell clone carrying the t(14;14) chromosomal translocation was known to be present for greater than 10 years before the onset of overt leukemia. One molecular rearrangement of the T-cell receptor alpha locus corresponded to a functional variable-joining region (V-J) joining, whereas the other derived from the breakpoint of the t(14;14)(q11;q32) translocation. Chromosomal in situ hybridization of the probe derived from the t(14;14) breakpoint localized the breakpoint region to 14q32.1, apparently the same region that is involved in another ataxia telangiectasia characteristic chromosome translocation, t(7;14)(q35;q32). The 14q32.1 breakpoint is at least 10,000 kilobase pairs (kbp) centromeric to the immunoglobulin heavy chain locus. Sequence analysis of the breakpoint indicates the involvement of a J alpha sequence during the translocation. Comigration of high-molecular weight DNA fragments involved with t(7;14) and t(14;14) translocations suggests the presence of a cluster of breakpoints in the 14q32.1 region, the site of a putative oncogene, TCL1.
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140.
G
G
Russo
M
M
Isobe
R
R
Gatti
J
J
Finan
O
O
Batuman
K
K
Huebner
P C
PC
Nowell
C M
CM
Croce
D000483:Alleles; D001260:Ataxia Telangiectasia / Q000150:complications / Q000235:genetics*; D001345:Autoradiography; D001483:Base Sequence; D015139:Blotting, Southern; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D015342:DNA Probes; D005260:Female; D006801:Humans; D015461:Leukemia, Prolymphocytic, T-Cell / Q000150:complications / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000648:ultrastructure*; D014178:Translocation, Genetic
D015342:DNA Probes; D004247:DNA