Heterogeneous breakpoints in patients with acute lymphoblastic leukemia and the dic(9;20)(p11-13;q11) show recurrent involvement of genes at 20q11.21

Qian An, Sarah L. Wright, Anthony V. Moorman, Helen Parker, Mike Griffiths, Fiona M. Ross, Teresa Davies, Christine J. Harrison, Jon C. Strefford

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1164-1169
Number of pages6
JournalHaematologica
Volume94
Issue number8
DOIs
StatePublished - Aug 2009
Externally publishedYes

Keywords

  • Acute lymphoblastic leukemia
  • Dic(9;20)
  • Fusion genes
  • Genetic target

ASJC Scopus subject areas

  • Hematology

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