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Lymphoma

p53 gene mutations are uncommon but p53 is commonly expressed in anaplastic large-cell lymphoma

Abstract

Anaplastic large-cell lymphoma (ALCL), as defined in the World Health Organization, is a heterogeneous category in which a subset of cases is associated with the t(2;5)(p23;q35) or variant translocations resulting in overexpression of anaplastic lymphoma kinase (ALK). p53 has not been assessed in currently defined subsets of ALCL tumors. In this study, we assessed ALK+ and ALK− ALCL tumors for p53 gene alterations using PCR, single-strand conformation polymorphism and direct sequencing methods. We also immunohistochemically assessed ALCL tumors for p53 expression. Three of 36 (8%) ALCL tumors (1/14 ALK+, 2/22 ALK−) with adequate DNA showed p53 gene mutations. By contrast, p53 was overexpressed in 36 of 55 (65%) ALCL tumors (16 ALK+, 20 ALK−). p21, a target of p53, was expressed in 15 of 31 (48%) ALCL tumors including seven of 15 (47%) p53-positive tumors. p21 expression in a subset of ALCL suggests the presence of functional p53 protein. Apoptotic rate was significantly higher in p53-positive than p53-negative tumors (mean 2.78 vs 0.91%, P=0.0003). We conclude that the p53 gene is rarely mutated in ALK+ and ALK− ALCL tumors. Nevertheless, wild-type p53 gene product is commonly overexpressed in ALCL and may be functional in a subset of these tumors.

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Acknowledgements

Dr GZ Rassidakis is a recipient of an Odyssey Program Special Fellowship from The University of Texas MD Anderson Cancer Center.

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Correspondence to L J Medeiros.

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This study was presented in part at the 93rd United States and Canadian Academy of Pathology meeting, Vancouver, BC, Canada, March 6–12, 2004

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu).

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Rassidakis, G., Thomaides, A., Wang, S. et al. p53 gene mutations are uncommon but p53 is commonly expressed in anaplastic large-cell lymphoma. Leukemia 19, 1663–1669 (2005). https://doi.org/10.1038/sj.leu.2403840

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