We investigated the effects of the germ-line single nucleotide polymorphisms TP53R72P (215G>C) and MDM2 SNP309 (-410T>G), and p53 protein expression in breast tumors on survival.
A higher prevalence of p53 mutations was found in the breast tumors of current smokers (36.5%; P = 0.02) compared with never smokers (23.6%), whereas fewer mutations were found in former smokers (16.2%; P = 0.09).
The frequency of abnormalities affecting chromosome 17p and the TP53 gene was determined in 27 breast tumours from 26 female patients carrying the Icelandic BRCA2 founder mutation (999del5).
This study aimed to objectively determine optimal thresholds for p53 positivity by manual and automated scoring methods using whole tissue sections from the Carolina Breast Cancer Study. p53-immunostained slides were available for 564 breast tumors previously assayed for TP53 mutations.
Furthermore, Notch-induced transcriptomes from p53 wild-type and -mutated breast tumor cell lines differed extensively, and for a subset of genes upregulated by Notch in a p53-mutant cell line, this upregulation was reduced by wild-type p53.
The tumour-suppressor gene TP53 is frequently mutated in breast tumours, and the majority of the mutations are clustered within the core domain, the region involved in DNA binding.
Mutations in the p53 tumor suppressor gene are frequent in breast tumors but the implication of p53 mutations in breast cancer development remains poorly understood.
1-kb segment of the p53 tumor suppressor gene (54.5% G+C) containing exons 5-9, including the intervening introns, was screened in a blinded analysis of 48 samples from human breast tumors containing known wild-type or mutant p53 genes.
A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer.
Immunohistochemical analysis of breast tumors from these patients revealed high levels of mutant p53 protein, suggesting a functional mutation in the p53 gene.
Impaired p53 function leads to centrosome amplification, acquired ERalpha phenotypic heterogeneity and distant metastases in breast cancer MCF-7 xenografts.
These results indicate that these biochemically defined domains also have biological relevance in terms of breast cancer disease course, and suggest that some mutations in TP53, more than others, can contribute to the development of clinically more aggressive and perhaps treatment resistant breast tumours.