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Spectrum of p53 mutations in low-grade B-cell malignancies

Leukemia volume 22, pages 1071–1073 (2008)Cite this article

There has been considerable interest in p53 mutation in low-grade B-cell malignancies over the years, particularly in chronic lymphocytic leukaemia (CLL). CLL exhibits a highly variable clinical course; p53 mutation confers a worse prognosis and adversely affects response to purine analogue therapy. Reported rates of mutation of the p53 gene in B-cell malignancies vary between studies and subtypes, but are not common.1 The majority of studies have restricted mutation screening to exons 5–8, so the true rate of mutation outside of this region is not known.

The non-isotopic RNase cleavage assay (NIRCA) works on the principle that RNase cleaves both strands of duplex RNA targets at mismatched bases and has been previously developed and validated as a method for screening for the presence of mutated p53 mRNA.2 Briefly single stranded RNA is synthesized from opposing strands of patient PCR product and wild type control product, of the entire p53 coding region (from viral promoter sequences incorporated during PCR) and opposing RNA strands are hybridized. Subsequent digestion with RNase and analysis by agarose gel electrophoresis and ethidium bromide staining results in the observation of digested product for those samples containing a mismatch between patient and wild type sequence. We have used NIRCA to screen the entire coding region of the p53 gene from 480 patients diagnosed with a low-grade B-cell malignancy for p53 mutations (see Table 1 for disease classification).

Table 1 Disease classification and p53 mutation rate
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Acknowledgements

This work was supported by The Musgrove Leukaemic Group Somerset.

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Authors and Affiliations

  1. Leukaemia Research Unit, Taunton and Somerset NHS Trust, Musgrove Park Hospital, Taunton, Somerset, UK

    T Bromidge & D Howe

  2. Department of Haematology, Taunton and Somerset NHS Trust, Musgrove Park Hospital, Taunton, Somerset, UK

    S Johnson

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  1. T Bromidge
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  2. S Johnson
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  3. D Howe
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Correspondence to T Bromidge.

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Bromidge, T., Johnson, S. & Howe, D. Spectrum of p53 mutations in low-grade B-cell malignancies. Leukemia 22, 1071–1073 (2008). https://doi.org/10.1038/sj.leu.2405002

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