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Chronic Lymphocytic Leukemia

TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations

Leukemia volume 24, pages 2072–2079 (2010)Cite this article

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Abstract

The TP53 mutation profile in chronic lymphocytic leukemia (CLL) and the correlation of TP53 mutations with allele status or associated molecular genetics are currently unknown. We performed a large mutation analysis of TP53 at four centers and characterized the pattern of TP53 mutations in CLL. We report on 268 mutations in 254 patients with CLL. Missense mutations appeared in 74% of cases compared with deletions and insertions (20%), nonsense (4%) and splice site (2%) mutations. The majority (243 of 268) of mutations were located in the DNA-binding domain. Transitions were found in 131 of 268 mutations, with only 41 occurring at methylated CpG sites (15%), suggesting that transitions at CpGs are uncommon. The codons most frequently mutated were at positions 175, 179, 248 and 273; in addition, we detected a common 2-nt deletion in the codon 209. Most mutations (199 of 259) were accompanied by deletion of the other allele (17p–). Interestingly, trisomy 12 (without 17p–) was only found in one of 60 cases with TP53 mutation (without 17p–) compared with 60 of 16 in the cohort without mutation (P=0.006). The mutational profile was not different in the cohorts with and without previous therapy, suggesting that the mechanism underlying the development of mutations may be similar, independent of treatment.

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Acknowledgements

The study was supported by Grant NS9858-3/2009 and NS10439-3/2009 provided by the Internal Grant Agency of the Ministry of Health of the Czech Republic and the German José Carreras Leukemia Foundation (R06/28v).

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Authors and Affiliations

  1. Department of Internal Medicine, University of Ulm, Ulm, Germany

    T Zenz, D Vollmer, H Helfrich, M Heuberger, P Hoth, M Fuge, T Denzel, S Häbe, H Döhner & S Stilgenbauer

  2. University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic

    M Trbusek, J Smardova, J Malcikova, P Kuglik, S Pospisilova & J Mayer

  3. Biostatistics, German Cancer Research Center, Heidelberg, Germany

    A Benner

  4. Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden

    T Soussi

  5. Université Pierre et Marie Curie-Paris6, Paris, France

    T Soussi

  6. Roche Molecular Systems, Pleasanton, CA, USA

    S Truong, N Patten & L Wu

  7. Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK

    D Oscier, R Ibbotson, A Gardiner & I Tracy

  8. Department of Haematology, University of Liverpool, Liverpool, UK

    K Lin & A Pettitt

  9. Department of Internal Medicine I, University of Cologne, Cologne, Germany

    M Hallek

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  1. T Zenz
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for the European Research Initiative on CLL (ERIC)

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Correspondence to T Zenz.

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Zenz, T., Vollmer, D., Trbusek, M. et al. TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations. Leukemia 24, 2072–2079 (2010). https://doi.org/10.1038/leu.2010.208

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