5′RUNX1-3′USP42 chimeric gene in acute myeloid leukemia can occur through an insertion mechanism rather than translocation and may be mediated by genomic segmental duplications

Molecular Cytogenetics

Francesco Albano¹  Giorgina Specchia¹  Cosimo Cumbo¹  Claudia Brunetti¹  Crescenzio Francesco Minervini¹  Angela Minervini¹  Angelo Cellamare¹  Paola Casieri¹  Giuseppina Tota¹  Nicoletta Coccaro¹  Luisa Anelli¹  Antonella Zagaria¹ 

[1] Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section - University of Bari, P.zza G. Cesare, Bari, 11 70124, Italy

关键词: Segmental duplications;    Insertion event;    Cancer genetics;    Acute myeloid leukemia;   

Others  :  1149762
DOI  :  10.1186/s13039-014-0066-7

 received in 2014-08-13, accepted in 2014-09-17,  发布年份 2014

【 摘 要 】

Background

The runt-related transcription factor 1 (RUNX1) gene is a transcription factor that acts as a master regulator of hematopoiesis and represents one of the most frequent targets of chromosomal rearrangements in human leukemias. The t(7;21)(p22;q22) rearrangement generating a 5?RUNX1-3?USP42 fusion transcript has been reported in two cases of pediatric acute myeloid leukemia (AML) and further in eight adult cases of myeloid neoplasms. We describe the first case of adult AML with a 5?RUNX1-3?USP42 fusion gene generated by an insertion event instead of chromosomal translocation.

Methods

Conventional and molecular cytogenetic analyses allowed the precise characterization of the chromosomal rearrangement and breakpoints identification. Gene expression analysis was performed by quantitative real-time PCR experiments, whereas bioinformatic studies were carried out for revealing structural genomic characteristics of breakpoint regions.

Results

We identified an adult AML case bearing a ins(21;7)(q22;p15p22) generating a 5?RUNX1-3?USP42 fusion gene on der(21) chromosome and causing USP42 gene over-expression. Bioinformatic analysis of the genomic regions involved in ins(21;7)/t(7;21) showed the presence of interchromosomal segmental duplications (SDs) next to the USP42 and RUNX1 genes, that may underlie a non-allelic homologous recombination between chromosome 7 and 21 in AML.

Conclusions

We report the first case of a 5?RUNX1-3?USP42 chimeric gene generated by a chromosomal cryptic insertion in an adult AML patient. Our data revealed that there may be a pivotal role for SDs in this very rare but recurrent chromosomal rearrangement.

【 授权许可】

   
2014 Zagaria et al.; licensee BioMed Central Ltd.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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