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

A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma
A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma
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.
0887-6924
1459-1465
Davies, A.J.
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Lee, A.M.
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Taylor, C.
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Clear, A.J.
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Goff, L.K.
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Iqbal, S.
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Cuthbert-Heavens, D.
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Calaminici, M.
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Norton, A.J.
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Lister, T.A.
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Fitzgibbon, J.
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Davies, A.J.
0fe6a40a-10d1-4ade-a7e6-d1dceb2470af
Lee, A.M.
b7a05220-1c96-4bf4-b1e2-8e03b1041823
Taylor, C.
f82de9c5-af37-4ca9-ab5b-261aed735756
Clear, A.J.
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Goff, L.K.
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Iqbal, S.
620f67bb-e2d0-4fc4-8887-f2474379cf79
Cuthbert-Heavens, D.
a7908d95-c595-498b-b5a3-6ed7c6ece171
Calaminici, M.
aaffc1c1-a95f-4119-9107-92f6d7ea6de0
Norton, A.J.
fe7d8253-bcfa-4789-9397-4001b795d75c
Lister, T.A.
ffe041c9-eb11-47e8-8c7c-177f8bc193c9
Fitzgibbon, J.
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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).

Record type: Article

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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Published date: 19 May 2005

Identifiers

Local EPrints ID: 73333
URI: http://eprints.soton.ac.uk/id/eprint/73333
ISSN: 0887-6924
PURE UUID: dc0cf26f-d44b-4874-8cd6-0680e864387f
ORCID for A.J. Davies: ORCID iD orcid.org/0000-0002-7517-6938

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Date deposited: 11 Mar 2010
Last modified: 03 Feb 2020 01:30

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Contributors

Author: A.J. Davies ORCID iD
Author: A.M. Lee
Author: C. Taylor
Author: A.J. Clear
Author: L.K. Goff
Author: S. Iqbal
Author: D. Cuthbert-Heavens
Author: M. Calaminici
Author: A.J. Norton
Author: T.A. Lister
Author: J. Fitzgibbon

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