Absence of point mutations at codon 17 of the Mdm2 gene (serine 17) in human primary tumors

Mdm2 is a phosphoprotein that interacts with protein p53, inhibiting its ac tivity. A serine located in position 17 of Mdm2, has been implicated in its phosphorylation process. We hypothesize that point mutations at serine 17 could block its phosphorylation and thereby increase the p53-Mdm2 interacti on. This mechanism could increase the p53 degradation and cause a loss of t he protective effect of p53 against tumorigenesis. This hypothesis was base d on recent studies in vitro, demonstrating that when serine 17 is mutated, the DNA-dependent protein kinase, activated by genomic damage, is unable t o phosphorylate it. Thus, we investigated whether structural point mutation s at exon 3 of the Mdm2 gene, affecting codon 17, were present in 162 human primary tumors, 70 breast carcinomas, 14 bladder tumors, 18 colon adenocar cinomas and 60 testicular tumors. Direct sequencing of a fragment (204 bp) of exon 3 of the Mdm2 gene that contains the codon 17 showed no mutations a t this position, independently of the presence or absence of p53 gene mutat ions in the same tumors. These results do not support the hypothesis that m utations in the Mdm2 gene at this level are involved in the tumorigenic pro cess of human cancers. (C) 2000 Elsevier Science B.V. All rights reserved.