title: Molecular cytogenetic detection of chromosomal breakpoints in T-cell receptor gene loci.
abstract: Chromosomal aberrations with breakpoints in T-cell receptor (TCR) gene loci are recurrent in several T-cell malignancies. Although the importance of interphase cytogenetics has been extensively shown in B-cell lymphomas, hardly any molecular cytogenetic tools are available for recurrent changes in T-cell disorders. Thus, we have established fluorescence in situ hybridization (FISH)-based break-apart assays for the TCRA/D (14q11), TCRB (7q34) and TCRG (7p14) genes and the TCL cluster (14q32). The assays were validated in normal controls as well as in 43 T-cell malignancies with cytogenetically proven 14q11, 7q34-35 or 7p13-21 aberrations. Breakpoints in TCRA/D, TCRB and TCRG could be diagnosed by these assays in 32/33 T-cell neoplasms with chromosome 14q11, 3/6 with 7q34-35 and 1/7 with 7p13-21 alterations, respectively. Application of the new FISH assays to a series of 24 angioimmunoblastic and 12 cutaneous T-cell lymphomas confirmed the cytogenetic evidence of lack of breakpoints in the TCRA/D or TCRB locus. Simultaneous detection of TCRA/D or TCRB breaks was achieved in a multicolor approach, which was further combined with detection of the T-cell-specific CD3 antigen in a multicolor FICTION (Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasm) assay. These new FISH and FICTION assays provide sensitive, rapid and accurate tools for the diagnosis and biological characterization of T-cell malignancies.
authors.affiliation: Institute of Human Genetics, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Gesk
authors.forename: J I
authors.initials: JI
authors.lastname: Martín-Subero
authors.forename: L
authors.initials: L
authors.lastname: Harder
authors.forename: B
authors.initials: B
authors.lastname: Luhmann
authors.forename: B
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: M J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: W
authors.initials: W
authors.lastname: Grote
authors.forename: R
authors.initials: R
authors.lastname: Siebert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002675:Child, Preschool; D019457:Chromosome Breakage; D007446:Chromosome Inversion; D020223:Chromosome Painting / Q000379:methods; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007621:Karyotyping; D015458:Leukemia, T-Cell / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D017384:Sequence Deletion; D012751:Sezary Syndrome / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta