Loss of chromosome 17p13 sequences and mutation of p53 in human breast carcinomas.

DNAs from ninety seven primary breast carcinoma biopsies have been examined for loss of sequences on 17p13. In addition, immunohistochemical analysis has been carried out on the majority of these cases to determine whether p53 gene expression can be detected. Detection of p53 expression is taken to indicate mutation of p53 leading to stabilisation of the protein and thus detectable levels of p53 in the cell. In 86% of breast carcinoma samples where both allele loss and expression data were available, loss of sequences on 17p13 and/or expression of p53 was detected. Alterations to p53, whether loss of one allele or mutation, are therefore by far the most common changes so far detected in primary human breast tumours. In three cases where expression of p53 could be detected by immunohistochemistry, the precise mutation to p53 was identified. All three mutations fall within the regions which are highly conserved in p53, encoded by exons 5 to 8. Two are single base changes leading to misense mutations, and the third is a single base-pair deletion. The expression of the latter gene would result in production of a truncated protein which should lack normal biological activities.