TP53 Mutation Analysis in Clinical Practice: Lessons From Chronic Lymphocytic Leukemia

Authors

  • Jitka Malcikova,

    1. Central European Institute of Technology, Center of Molecular Medicine, and Faculty of Medicine, Department of Internal Medicine – Hematology and Oncology, Masaryk University, Brno, Czech Republic
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  • Sarka Pavlova,

    1. Central European Institute of Technology, Center of Molecular Medicine, and Faculty of Medicine, Department of Internal Medicine – Hematology and Oncology, Masaryk University, Brno, Czech Republic
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  • Katerina Stano Kozubik,

    1. Central European Institute of Technology, Center of Molecular Medicine, and Faculty of Medicine, Department of Internal Medicine – Hematology and Oncology, Masaryk University, Brno, Czech Republic
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  • Sarka Pospisilova

    Corresponding author
    1. Central European Institute of Technology, Center of Molecular Medicine, and Faculty of Medicine, Department of Internal Medicine – Hematology and Oncology, Masaryk University, Brno, Czech Republic
    • Correspondence to: Sarka Pospisilova, Central European Institute of Technology, Center of Molecular Medicine, Kamenice 5, 625 00 Brno, Czech Republic. E-mail: sarka.pospisilova@ceitec.muni.cz

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  • For the TP53 Special Issue

  • Contract grant sponsors: Central European Institute of Technology (MSMT CR CZ.1.05/1.1.00/02.0068); FP7-HEALTH-2012-INNOVATION-1 (306242); MSMT 2013-2015, no. 7E13008; Internal Grant Agency, Ministry of Health, Czech Republic (IGA MZ CR NT13493-4/2012, NT13519-4/2012).

ABSTRACT

In leukemia, TP53 mutations are not frequent but clearly associate with impaired survival and therapy response. Here, we describe the biological and clinical consequences of TP53 dysfunction as well as the methodical aspects of TP53 analysis in chronic lymphocytic leukemia (CLL). In CLL, TP53 defects are routinely analyzed as part of disease prognostication. Deletions of TP53 locus (17p) have been uniformly detected using I-FISH for several years. Since monoallelic mutations have also been shown to have negative prognostic impact, it is recommended to examine both TP53 mutations and deletions. Several methods are used to detect TP53 mutations, and next-generation sequencing (NGS) is becoming a convenient option for routine analysis. Besides this, ultradeep NGS permits the detection of minor clones carrying TP53 mutations, even below 1%. The prognostic impact of minor TP53-defective subclones is currently unknown, nevertheless they unequivocally bear the risk of being selected by therapy. Prospective studies assessing the consequences of carrying such clones are in progress.

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