p53 mutations and overexpressions in Japanese breast cancer.
Mutations in the p53 gene were analysed in 50 cases with breast cancer by PCR-SSCP and direct DNA sequencing. Mutations were found in 10 of 50 cases (20%) including a case with Tis, and loss of the normal allele was found in five of these cases. Eight of the 10 mutations occurred within highly conserved domains, but no mutational hot spots were found. GC to AT transitions were the most frequent mutations (six of 10 cases), while mutations at CpG dinucleotides were found in three cases (30%). AT to TA transversions were the second most frequent mutation (20%). The level of expression of p53 protein was assessed by Western blot analysis in 62 cases. Overexpression of p53 protein was detected in 21 of 62 cases (34%) including a case with Tis. There was a strong correlation between missense mutations in the p53 gene and overexpression of p53 protein. Overexpression of p53 protein was closely associated with increasing tumour size and ER-negative status among the various factors investigated, suggesting that p53 overexpression may reflect the lack of differentiation in breast cancer.
Fukushima
T
T
Department of Surgery, Fukushima Medical College, Japan.
Onda
M
M
Abe
R
R
Otake
T
T
Kimijima
I
I
Tsuchiya
A
A
D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D016159:Tumor Suppressor Protein p53