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Title: Breakpoint of an inversion of chromosome 14 in a T-cell leukemia: sequences downstream of the immunoglobulin heavy chain locus are implicated in tumorigenesis

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)

T-cell tumors are characterized by inversions or translocations of chromosome 14. The breakpoints of these karyotypic abnormalities occur in chromosome bands 14q11 and 14q32 - the same bands in which the T-cell receptor (TCR) ..cap alpha..-chain and immunoglobulin heavy chain genes have been mapped, respectively. Patients with ataxia-telangiectasia are particularly prone to development of T-cell chronic lymphocytic leukemia with such chromosomal abnormalities. The authors describe DNA rearrangements of the TCR ..cap alpha..-chain gene in an ataxia-telangiectasia-associated leukemia containing both a normal and an inverted chromosome 14. The normal chromosome 14 has undergone a productive join of TCR ..cap alpha..-chain variable (V/sub ..cap alpha../) and joining (J/sub ..cap alpha../) gene segments. The other allele of the TCR ..cap alpha..-chain gene features a DNA rearrangement, about 50 kilobases from the TCR ..cap alpha..-chain constant (C/sub ..cap alpha../) gene, that represents the breakpoint of the chromosome 14 inversion; this breakpoint is comprised of a TCR J/sub ..cap alpha../) segment (from 14q11) fused to sequences derived from 14q32 but on the centromeric side of C/sub ..mu../. These results imply that 14q32 sequences located at an undetermined distance downstream of immunoglobulin C/sub ..mu../ locus can contribute to the development of T-cell tumors.

Research Organization:
Medical Research Council Laboratory of Molecular Biology, Cambridge (England)
OSTI ID:
6408595
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:24
Country of Publication:
United States
Language:
English

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