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 of genetic alterations found in diverse types of human cancer. The majority of the mutations occur in the core domain, which contains the sequence-specific DNA-binding site. They may result in loss of DNA binding and disability of transcriptional activation of genes involved in cell-cycle regulation. Analysis of the protein-structure model of these mutations can provide clues to the function of specific regions of p53 and to the clinical significance of p53 mutation. We examined 68 cases of pancreatic adenocarcinoma for p53 mutation and mutant protein-structure model by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP), PCR-DNA sequencing, and computer-generated protein modeling. Twenty (29.41%) of 68 cases showed p53 mutation. Statistical analysis showed there was no significant difference in survival between p53 mutation and wild-type p53 (median survival, 12 vs. 13 months; p = 0.2034). Among p53 mutations, nine mutations were located 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 survival compared with those with mutation far from the DNA-binding site (median survival, 5 vs. 15 months; p = 0.0435). We conclude that detecting and modeling the p53 gene mutation may be used as a tool in predicting the clinical course of patients diagnosed with pancreatic adenocarcinoma.
Li
Y
Y
Department of Pathology, Wayne State University School of Medicine, Harper Hospital, Detroit Medical Center, Michigan 48201, USA.
Bhuiyan
M
M
Vaitkevicius
V K
VK
Sarkar
F H
FH
D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D005260:Female; D016368:Frameshift Mutation; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017433:Protein Structure, Secondary; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics*
D016159:Tumor Suppressor Protein p53