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.
Immunohistochemical analysis of breast tumors from these patients revealed high levels of mutant p53 protein, suggesting a functional mutation in the p53 gene.
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.
Our data indicate that p53 mutations are frequent in breast tumours associated with unfavorable prognosis, including high-grade or the comedo histotype.
It is known that both genetic and environmental factors are important for breast carcinogenesis and that structural and/or functional alterations at p53 gene are commonly observed in breast tumors.
The principal aim of this study was to study the concordance of RNA- and DNA-based direct sequencing methods in detecting p53 mutations in breast tumors.
The p53 gene mutations have been associated with the development of human breast and canine mammary neoplasms; breast carcinoma patients with alterations of p53 gene are considered to have a poor prognosis.
We found that the high incidence of protein truncating TP53 mutations and the pattern and amount of genomic aberrations specific for BRCA1-mutated breast tumors are also characteristic for BLBCs and different from luminal breast tumors.