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Clinical significance of TP53 mutation in myeloma

Leukemia volume 21, pages 582–584 (2007)Cite this article

The p53 tumor suppressor is a critical regulator of tissue homeostasis, and its inactivation at the gene or protein level confers cellular properties conducive for oncogenesis and cancer progression. Furthermore, p53 inactivation has been associated with resistance to therapy. Indeed, the p53 response is deficient in >50% of cancers mainly through gene mutation.1 In contrast to other solid tumors and carcinomas, TP53 mutations are rare in multiple myeloma (MM), a malignancy characterized by clonal plasma cells secreting monoclonal immunoglobulin.2 Previous studies of TP53 mutations in MM were hampered by clinical heterogeneity in the study cohorts and the relatively small sample size (all with <100 patients). These studies reported a prevalence of TP53 mutation ranging from 0 to 20%.2 However, it is not always obvious whether the study cohorts consist of newly diagnosed or relapsed patients. This is important as the prevalence of TP53 mutations increases with more advance disease (even this is not clearly defined and seemed to include Durie–Salmon stage III and plasma cell leukemia) and is very prevalent in HMCLs.2 Furthermore, these studies generally limit their investigation to exons 5–9, whereas several studies in other cancers have shown that mutations can occur in other exons.1 At present, the prognostic importance of TP53 mutations in myeloma is unknown.

In this study, we comprehensively define the prevalence of TP53 mutations in newly diagnosed myeloma patients by screening genomic DNA from unsorted whole bone marrow from a large cohort of patients entered into an Eastern Cooperative Oncology Group clinical trial E9486/E9487 (n=561) using conformation sensitive gel electrophoresis (CSGE). A total of 268 patients, based on sample availability, were included in our current study. These patients had extensive follow-up information with median follow-up of survivors 4.8 years and only 4.5% (n=25) of the cohort alive at the time of our analysis, resulting in negligible censoring. Fluorescent in situ hybridization (FISH) studies using the cytoplasmic immunoglobulin-FISH technique in this cohort of patients has been previously reported.3

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Authors and Affiliations

  1. Division of Hematology-Oncology, Mayo Clinic Scottsdale, Scottsdale, AZ, USA

    W J Chng, S Van Wier & R Fonseca

  2. Division of Hematology, Mayo Clinic Rochester, Rochester, MN, USA

    T Price-Troska, N Gonzalez-Paz, K Henderson, P Greipp & S V Rajkumar

  3. Eastern Cooperative Oncology Group Statistical Center, Dana Farber Cancer Institute, Boston, MA, USA

    S Jacobus & E Blood

  4. Department of Oncology, North Memorial Cancer Center, Minneapolis, MN, USA

    M Oken

  5. Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA. E-mail: fonseca.rafael@mayo.edu,

    B Van Ness

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  1. W J Chng
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Chng, W., Price-Troska, T., Gonzalez-Paz, N. et al. Clinical significance of TP53 mutation in myeloma. Leukemia 21, 582–584 (2007). https://doi.org/10.1038/sj.leu.2404524

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