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

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Abstract
T-cell tumors are characterized inversions or translocations of chromosome 14. The breakpoints of these karyotypic abnormalities occur in chromosome bands 14q11 and 14q32.sbd.the same bands in which the T-cell receptor (TCR) .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. We now describe DNA rearrangements of the TCR .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 TCE .alpha.-chain variable (V.alpha.) and joining (J.alpha.) gene segments. The other allele of the TCR .alpha.-chain gene features a DNA rearrangement, about 50 kilobases from the TCR .alpha.-chain constant (C.alpha.) gene, that represents the breakpoint of the chromosome 14 inversion; this breakpoint is comprised of a TCR J.alpha. segment (from 14q11) fused to sequences derived from 14q32 but on the centromeric side of C.mu.. These results imply that 14q32 sequences located at an undetermined distance downstream of the immunoglobulin C.mu. locus can contribute to the development of T-cell tumors.