Microhomologies and topoisomerase II consensus sequences identified near the breakpoint junctions of the recurrent t(7;21)(p22;q22) translocation in acute myeloid leukemia
✍ Scribed by Amélie Giguère; Josée Hébert
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 839 KB
- Volume
- 50
- Category
- Article
- ISSN
- 1045-2257
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✦ Synopsis
Abstract
RUNX1 rearrangements are common genetic abnormalities in acute leukemia. The t(7;21)(p22;q22) translocation, recently described in three cases of myeloid neoplasias, fuses the ubiquitin specific peptidase 42 gene, USP42, a member of the deubiquitinating enzyme family, to RUNX1. In this study, we characterized the semicryptic t(7;21)(p22;q22) translocation, identified by fluorescent in situ hybridization and spectral karyotyping, in a novel case of acute myeloid leukemia. Sequence analysis of the reverse transcription‐polymerase chain reaction products confirmed the presence of two in‐frame RUNX1‐USP42 and one reciprocal in‐frame USP42‐RUNX1 fusion transcripts. Bioinformatic analysis of the genomic translocation breakpoints revealed microhomologies and insertion of shared nucleotides at the junctions. A topoisomerase II sequence was also detected near the break site. Additionally, we demonstrated a significant overexpression of the rearranged USP42 gene in t(7;21) positive cells using quantitative real‐time PCR. Our results provide the first evidence of the possible involvement of the nonhomologous end‐joining mechanism in the origin of the recurrent t(7;21) translocation. Moreover, presence of the complete catalytic USP site in the putative chimeric proteins and the upregulated expression of USP42 suggest a role of the deubiquitinating enzyme in the pathogenesis of this leukemia. © 2011 Wiley‐Liss, Inc.