title: 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.
abstract: 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) 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 TCR 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.
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics*; D001483:Base Sequence; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D007446:Chromosome Inversion; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D005803:Genes, Immunoglobulin; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D007938:Leukemia / Q000235:genetics*; D008969:Molecular Sequence Data
chemical_list: D007148:Immunoglobulin mu-Chains