Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

TP53 mutations in myeloid malignancies are either homozygous or hemizygous due to copy number-neutral loss of heterozygosity or deletion of 17p

Leukemia volume 24, pages 216–219 (2010)Cite this article

Our previous studies showed that single nucleotide polymorphism arrays (SNP-As), applied as a karyotyping platform, complement traditional metaphase cytogenetics (MCs) and improve the diagnostic yield of cytogenetic studies, as SNP-A can more precisely resolve smaller genetic defects and allow for detection of copy number-neutral loss of heterozygosity (CN-LOH), a defect frequently found in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Like balanced translocations, CN-LOH represents a chromosomal abnormality that occurs without a concurrent change in gene copy number. CN-LOH is an increasingly recognized chromosomal mechanism by which homozygous somatic mutations may be acquired during evolution of hematological malignancies and can pinpoint the location of such gene(s); examples include CEBPA, FLT3, WT1, RUNX1, JAK2 and NF1.1

Deletions involving the short arm of chromosome 17, detectable by MC in MDS and AML, may be associated with a complex karyotype that includes –5/5q- and/or –7/7q-; such patients have a poor prognosis.2 The well-known tumor suppressor gene TP53, located at 17p13.1, is a likely candidate gene contributing to the disease phenotype after mutation of one or both alleles. Mutations may be linked to loss of 17p by chromosomal or submicroscopic deletion LOH (mut/–) or may occur in the absence of 17p loss in either heterozygous (wt/mut), biallelic (mut1/mut2) or homozygous (mut1/mut1) forms through CN-LOH. Although mutations in TP53 are frequent in solid tumors, the mutation frequency reported in hematological malignancies is much lower.2

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Maciejewski JP, Mufti GJ . Whole genome scanning as a cytogenetic tool in hematologic malignancies. Blood 2008; 112: 965–974.

    Article  CAS  Google Scholar 

  2. Lai JL, Preudhomme C, Zandecki M, Flactif M, Vanrumbeke M, Lepelley P et al. Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoiesis and a high incidence of P53 mutations. Leukemia 1995; 9: 370–381.

    CAS  Google Scholar 

  3. Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P et al. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat 2007; 28: 622–629.

    Article  CAS  Google Scholar 

  4. Wilentz RE, Argani P, Hruban RH . Loss of heterozygosity or intragenic mutation, which comes first? Am J Pathol 2001; 158: 1561–1563.

    Article  CAS  Google Scholar 

  5. Christiansen DH, Andersen MK, Pedersen-Bjergaard J . Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol 2001; 19: 1405–1413.

    Article  CAS  Google Scholar 

  6. Bowen D, Groves MJ, Burnett AK, Patel Y, Allen C, Green C et al. TP53 gene mutation is frequent in patients with acute myeloid leukemia and complex karyotype, and is associated with very poor prognosis. Leukemia 2009; 23: 203–206.

    Article  CAS  Google Scholar 

  7. Haferlach C, Dicker F, Herholz H, Schnittger S, Kern W, Haferlach T . Mutations of the TP53 gene in acute myeloid leukemia are strongly associated with a complex aberrant karyotype. Leukemia 2008; 22: 1539–1541.

    Article  CAS  Google Scholar 

  8. Alvarez S, Cigudosa JC . Gains, losses and complex karyotypes in myeloid disorders: a light at the end of the tunnel. Hematol Oncol 2005; 23: 18–25.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported in part by RO1HL-082983, U54 RR019391 K24 HL-077522 and by Grant from AA&MDS International Foundation and Robert Duggan Charitable Fund (JPM).

Author information

Authors and Affiliations

  1. Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

    M Jasek, L P Gondek, N Bejanyan, R Tiu, J Huh, C O'Keefe & J P Maciejewski

  2. Department of Laboratory Medicine, Ewha Womans University, School of Medicine, Seoul, South Korea

    J Huh

  3. Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA

    K S Theil

  4. Divisions of Hematology and Hematological Malignancy, Departments of Medicine and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    M A McDevitt

  5. Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

    J P Maciejewski

Authors
  1. M Jasek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L P Gondek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N Bejanyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R Tiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Huh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K S Theil
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C O'Keefe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M A McDevitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J P Maciejewski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J P Maciejewski.

Additional information

Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jasek, M., Gondek, L., Bejanyan, N. et al. TP53 mutations in myeloid malignancies are either homozygous or hemizygous due to copy number-neutral loss of heterozygosity or deletion of 17p. Leukemia 24, 216–219 (2010). https://doi.org/10.1038/leu.2009.189

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2009.189

This article is cited by

Search

Advanced search

Quick links