p53 tumor suppressor gene mutations in transformed cutaneous T‐cell lymphoma: A study of 12 cases

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Abstract
The transformation of cutaneous T‐cell lymphoma (t‐CTCL) is an uncommon phenomenon that is associated with histopathologic changes and follows an aggressive course. The factors contributing to this transformation are poorly understood. The aim of this study was to analyze the p53 status in t‐CTCL and to correlate il with disease outcome. The p53 status was investigated by immunohistochemistry, single‐strand conformation polymorphism (SSCP) and DNA sequencing in 12 patients with t‐CTCL. Eight mutations were detected; including four in exon 5, one in exon 6 and three in exon 7. Five were point mutations and three were deletions. Paired samples from nontransformed patch and plaque lesions showed no p53 over‐expression. Eight disease‐related deaths were reported, six to 23 months after transformation, all of which had p53 mutations. Three other patients with wild phenotype (WT‐p53) were last reported alive with the disease 19‐33 months after transformation (p<0.0002). One other case had a p53 mutation but a short period of follow‐up. Our results suggest that phenotypic changes of t‐CTCL are frequently associated with genotype alterations in the p53 gene. Because 70% of the mutations detected were either G to C transversions or deletions, nucleoidepairing mismatch and not DNA damage by UVB represents a likely mechanism for mutagenesis. Furthermore, the data may help in the design of gene transfer therapies that target the p53 molecule.