Display options
Cite
Zagaria A, Anelli L, Coccaro N, et al. 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. Mol Cytogenet. 2014;7(1):66doi: 10.1186/s13039-014-0066-7.
Zagaria, A., Anelli, L., Coccaro, N., Tota, G., Casieri, P., Cellamare, A., Minervini, A., Minervini, C. F., Brunetti, C., Cumbo, C., Specchia, G., & Albano, F. (2014). 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, 7(1), 66. https://doi.org/10.1186/s13039-014-0066-7
Zagaria, Antonella, et al. "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 vol. 7,1 (2014): 66. doi: https://doi.org/10.1186/s13039-014-0066-7
Zagaria A, Anelli L, Coccaro N, Tota G, Casieri P, Cellamare A, Minervini A, Minervini CF, Brunetti C, Cumbo C, Specchia G, Albano F. 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. Mol Cytogenet. 2014 Oct 01;7(1):66. doi: 10.1186/s13039-014-0066-7. eCollection 2014. PMID: 25298786; PMCID: PMC4189616.
Copy Download .nbib Format: NLM
Share it on

Mol Cytogenet. 2014 Oct 01;7(1):66. doi: 10.1186/s13039-014-0066-7. eCollection 2014.

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

Antonella Zagaria, Luisa Anelli, Nicoletta Coccaro, Giuseppina Tota, Paola Casieri, Angelo Cellamare, Angela Minervini, Crescenzio Francesco Minervini, Claudia Brunetti, Cosimo Cumbo, Giorgina Specchia, Francesco Albano

Affiliations

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

PMID: 25298786 PMCID: PMC4189616 DOI: 10.1186/s13039-014-0066-7

Abstract

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.

Keywords: Acute myeloid leukemia; Cancer genetics; Insertion event; Segmental duplications

References

  1. Oncogene. 2010 Apr 29;29(17):2509-16 - PubMed
  2. Blood. 1997 Jul 15;90(2):489-519 - PubMed
  3. Oncol Rep. 2013 Oct;30(4):1549-52 - PubMed
  4. Br J Haematol. 1994 Jun;87(2):409-12 - PubMed
  5. Br J Haematol. 1996 Sep;94(3):557-73 - PubMed
  6. Nat Rev Genet. 2006 Jul;7(7):552-64 - PubMed
  7. Gene Expr Patterns. 2007 Jan;7(1-2):143-8 - PubMed
  8. Science. 1990 Jan 5;247(4938):64-9 - PubMed
  9. Curr Opin Genet Dev. 2009 Jun;19(3):196-204 - PubMed
  10. Leukemia. 2006 Feb;20(2):224-9 - PubMed
  11. Cancer Genet. 2012 Jul-Aug;205(7-8):365-72 - PubMed
  12. Genome Res. 2004 Nov;14(11):2209-20 - PubMed
  13. Genes Chromosomes Cancer. 2004 Sep;41(1):86-91 - PubMed
  14. Br J Haematol. 2014 Aug;166(3):449-52 - PubMed
  15. J Immunol. 2008 Apr 1;180(7):4402-8 - PubMed
  16. BMC Genomics. 2014 Jun 29;15:537 - PubMed
  17. Trends Genet. 1998 Oct;14(10):417-22 - PubMed
  18. Am J Hum Genet. 2004 Jan;74(1):1-10 - PubMed
  19. Exp Hematol Oncol. 2014 Mar 19;3:8 - PubMed
  20. Genes Chromosomes Cancer. 2011 Apr;50(4):228-38 - PubMed
  21. Anticancer Res. 2009 Apr;29(4):1031-7 - PubMed
  22. EMBO J. 2011 Nov 15;30(24):4921-30 - PubMed
  23. J Cell Physiol. 2010 Jan;222(1):50-6 - PubMed
  24. Mol Biol Evol. 2005 Jan;22(1):135-41 - PubMed
  25. Br J Haematol. 2010 Mar;148(6):938-43 - PubMed

Publication Types