title: Detection of translocations involving the HOX11/TCL3-locus in 10q24 by interphase fluorescence in situ hybridization.
abstract: The t(10;14)(q24;q11) and its variant t(7;10)(q35;q24), which are recurrent in acute T-cell leukemia, lead to activation of the HOX11/TCL3-gene in chromosomal region 10q24 by juxtaposing this gene to one of the T-cell receptor loci. In the present study, we established a diagnostic assay for detecting these translocations by interphase fluorescence in situ hybridization (FISH). BAC clones flanking the HOX11/TCL3-locus were obtained from a fingerprinted BAC-contig of chromosomal region 10q24. BAC clones located proximal and distal of the HOX11/TCL3-locus were differently labeled and applied to interphase-FISH in seven normal controls and eight T-cell neoplasms with t(10;14)(q24;q11) or t(7;10)(q35;q24). In over 1600 nuclei of controls, a considerable split defined as separation of each one signal for the proximal and distal probe by more than three times the signal diameter was observed in only one cell. In contrast, all T-cell neoplasms with t(10;14) or t(7;10) contained at least 47% of nuclei with a signal split indicating a breakpoint in the HOX11/TCL3-locus. Thus, the established double-color FISH approach provides a new reliable and routinely applicable tool for diagnosing breakpoints in the HOX11/TCL3-locus.
authors.affiliation: Institute of Human Genetics, University Hospital Kiel, Schwanenweg 24, D-24105 Kiel, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kahl
authors.forename: S
authors.initials: S
authors.lastname: Gesk
authors.forename: L
authors.initials: L
authors.lastname: Harder
authors.forename: J
authors.initials: J
authors.lastname: Harbott
authors.forename: L
authors.initials: L
authors.lastname: French
authors.forename: P
authors.initials: P
authors.lastname: Deloukas
authors.forename: W
authors.initials: W
authors.lastname: Grote
authors.forename: B
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: R
authors.initials: R
authors.lastname: Siebert
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D014178:Translocation, Genetic
chemical_list: D018398:Homeodomain Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C071250:TLX1 protein, human