A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma

Davies, A.J., Lee, A.M., Taylor, C., Clear, A.J., Goff, L.K., Iqbal, S., Cuthbert-Heavens, D., Calaminici, M., Norton, A.J., Lister, T.A. and Fitzgibbon, J. (2005) A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma. Leukemia, 19 (8), 1459-1465. (doi:10.1038/sj.leu.2403802).

Abstract

The role of TP53 mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre- and post-transformation. The entire TP53 coding sequence was screened and immunocytochemistry performed to determine expression of p53 and its key regulator MDM2. A total of 10 mutations were detected in eight patients (28%), although none were present at FL diagnosis. Mutations were not detected solely at the time of transformation; in three patients, mutated TP53 arose in at least one antecedent FL sample (6 months, 2.5 years and 4 years prior to transformation). Loss of heterozygosity at the TP53 locus occurred in 2/20 informative patients (only in t-FL samples). p53 staining was positive in 82% (9/11) of available biopsies with a missense mutation, and negative in 71% (45/63) with wtTP53. MDM2 expression was significantly higher in t-FL samples (mean 72% positive; 95% confidence interval (95% CI) 68–76%) than FL (mean 58% positive; 95% CI 54–62%) (P<0.001) but did not correlate with TP53 status. TP53 mutation has only a limited role in the transformation of FL, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent and may provide a more rational therapeutic target.

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Contributors

Author: A.J. Davies

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