title: Heterogeneous breakpoints in patients with acute lymphoblastic leukemia and the dic(9;20)(p11-13;q11) show recurrent involvement of genes at 20q11.21.
abstract: The dic(9;20)(p11-13;q11) is a recurrent chromosomal abnormality in patients with acute lymphoblastic leukemia. Although it results in loss of material from 9p and 20q, the molecular targets on both chromosomes have not been fully elucidated. From an initial cohort of 58 with acute lymphoblastic leukemia patients with this translocation, breakpoint mapping with fluorescence in situ hybridization on 26 of them revealed breakpoint heterogeneity of both chromosomes. PAX5 has been proposed to be the target gene on 9p, while for 20q, FISH analysis implicated the involvement of the ASXL1 gene, either by a breakpoint within (n=4) or centromeric (deletion, n=12) of the gene. Molecular copy-number counting, long-distance inverse PCR and direct sequence analysis identified six dic(9;20) breakpoint sequences. In addition to the three previously reported: PAX5-ASXL1, PAX5-C20ORF112 and PAX5-KIF3B; we identified three new ones in this study: sequences 3' of PAX5 disrupting ASXL1, and ZCCHC7 disrupted by sequences 3' of FRG1B and LOC1499503. This study provides insight into the breakpoint complexity underlying dicentric chromosomal formation in acute lymphoblastic leukemia and highlights putative target gene loci.
authors: Cancer Sciences Division, University of Southampton, Southampton, UK.
authors: Qian
authors: Q
authors: An
authors: Sarah L
authors: SL
authors: Wright
authors: Anthony V
authors: AV
authors: Moorman
authors: Helen
authors: H
authors: Parker
authors: Mike
authors: M
authors: Griffiths
authors: Fiona M
authors: FM
authors: Ross
authors: Teresa
authors: T
authors: Davies
authors: Christine J
authors: CJ
authors: Harrison
authors: Jon C
authors: JC
authors: Strefford
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002503:Centromere / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D051757:PAX5 Transcription Factor / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D016601:RNA-Binding Proteins; D012008:Recurrence; D012097:Repressor Proteins / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: C473949:ASXL1 protein, human; C101270:FRG1 protein, human; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C545342:ZCCHC7 protein, human