title: Analysis of a T-cell tumor-specific breakpoint cluster at human chromosome 14q32.
abstract: Cytogenetic abnormalities involving chromosome 14 band q32 are consistently observed in human T-cell tumors. Patients with ataxia-telangiectasia (AT) are especially prone to development of these tumors, which frequently carry either inversion inv(14)(q11;q32) or translocation t(14;14) (q11;q32) chromosomes. We have previously shown that the cytogenetic breakpoints of one t(14;14)(q11;q32) chromosome and two inv(14)(q11;q32) chromosomes in T-cell tumors from AT and non-AT patients join the T-cell receptor alpha chain locus, at chromosome band 14q11, with a region(s) at 14q32 centromeric of the immunoglobulin heavy chain variable region (VH) gene IGHV. We now show that these two inv(14) breakpoints are linked by 2.1 kb of germ-line 14q32 DNA and that the three breakpoints define, by in situ hybridization analysis, a single locus at chromosome band 14q32.1 located about 15-20 million base pairs on the centromeric side of the IGH locus. Sequence analysis of the 14q32.1 breakpoint regions indicates that abnormal recombination does not universally result from mistaken V-D-J joining (D = diversity region; J = joining region). Therefore, we invoke a tumor selection model to describe the role of the 14q32.1 locus in tumor development.
authors.affiliation: Laboratory of Molecular Biology, University of Cambridge, England.
authors.forename: L
authors.initials: L
authors.lastname: Mengle-Gaw
authors.forename: D G
authors.initials: DG
authors.lastname: Albertson
authors.forename: P D
authors.initials: PD
authors.lastname: Sherrington
authors.forename: T H
authors.initials: TH
authors.lastname: Rabbitts
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D015458:Leukemia, T-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D014178:Translocation, Genetic