title: Disruption of the RanBP17/Hox11L2 region by recombination with the TCRdelta locus in acute lymphoblastic leukemias with t(5;14)(q34;q11).
abstract: The t(5;14)(q33-34;q11) translocation constitutes a recurrent rearrangement in acute lymphoblastic leukemia involving the T cell receptor (TCR) delta locus on chromosome 14. Breakpoint sequences of the derivative chromosome 5 were isolated by application of a ligation-mediated PCR technique using TCR delta-specific primers to amplify genomic DNA from the leukemic cells of a patient with t(5;14). Through exon trap analysis, we identified various putative exons of the chromosome 5 target gene of the translocation; compilation of sequence information of trapped exons and available expressed sequence tags (ESTs) from the GenBank database allowed us to assemble 1.2 kb of the cDNA. Full-length cDNAs were isolated from a human testis cDNA library and sequence analysis predicted a putative Ran binding protein, a novel member of the importin-beta superfamily of nuclear transport receptors, called RanBP17. The t(5;14) breakpoint maps to the 3' coding region of the gene. The breakpoint of a second t(5;14) positive patient was mapped about 8 kb downstream of the most 3' RanBP17 exon and 2 kb upstream of the first exon of the orphan homeobox gene, Hox11L2. In both cases TCR delta enhancer sequences are juxtaposed downstream of the truncated or intact RanBP17 gene, respectively on the derivative chromosome.
authors.affiliation: University of Ulm, Section of Molecular Biology, Department of Pediatrics II, Germany.
authors.forename: T E
authors.initials: TE
authors.lastname: Hansen-Hagge
authors.forename: M
authors.initials: M
authors.lastname: Schäfer
authors.forename: H
authors.initials: H
authors.lastname: Kiyoi
authors.forename: S W
authors.initials: SW
authors.lastname: Morris
authors.forename: J A
authors.initials: JA
authors.lastname: Whitlock
authors.forename: P
authors.initials: P
authors.lastname: Koch
authors.forename: I
authors.initials: I
authors.lastname: Bohlmann
authors.forename: C
authors.initials: C
authors.lastname: Mahotka
authors.forename: C R
authors.initials: CR
authors.lastname: Bartram
authors.forename: J W G
authors.initials: JW
authors.lastname: Janssen
mesh_terms: D000208:Acute Disease; D015139:Blotting, Southern; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005091:Exons / Q000235:genetics; D015723:Gene Library; D019676:Genes, T-Cell Receptor delta / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D015513:Oncogene Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm / Q000032:analysis; D011995:Recombination, Genetic / Q000235:genetics*; D013737:Testis / Q000378:metabolism; D014178:Translocation, Genetic; D020931:ran GTP-Binding Protein / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; C417257:RanGTP-binding protein 17; C489494:TLX3 protein, human; C071250:TLX1 protein, human; D020931:ran GTP-Binding Protein