Structural alteration of p53 protein correlated to survival in patients with pancreatic adenocarcinoma

Mutations in the p53 tumor-suppressor gene represent the most common form o f genetic alterations found in diverse types of human cancer. The majority of the mutations occur in the core domain, which contains the sequence-spec ific DNA-binding site. They may result in loss of DNA binding and disabilit y of transcriptional activation of genes involved in cell-cycle regulation. Analysis of the protein-structure model of these mutations can provide clu es to the function of specific regions of p53 and to the clinical significa nce of p53 mutation. We examined 68 cases of pancreatic adenocarcinoma for p53 mutation and mutant protein-structure model by polymerase chain reactio n-single-strand conformational polymorphism (PCR-SSCP), PCR-DNA sequencing, and computer-generated protein modeling. Twenty (29.41%) of 68 cases showe d p53 mutation. Statistical analysis showed there was no significant differ ence in survival between p53 mutation and wild-type p53 (median survival, 1 2 vs. 13 months; p = 0.2034). Among p53 mutations, nine mutations were loca ted at or near the DNA-binding site, and the protein structures of the DNA- binding site were changed. Patients in this group had a shorter median surv ival compared with those with mutation far from the DNA-binding site (media n survival, 5 vs. 15 months; p = 0.0435). We conclude that detecting and mo deling the p53 gene mutation may be used as a tool in predicting the clinic al course of patients diagnosed with pancreatic adenocarcinoma.