Loss of heterozygosity on chromosome 17 and p53 mutation in primary human breast cancer

• Main Author: Coles, Christopher
• Published: University of Edinburgh 1994
• Subjects: 616.042
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.643329

A high frequency of LOH (61%) has been detected in a series of breast tumours at a site at a 17p13.3 suggesting the presence of a tumour suppressor gene involved in breast cancer on chromosome 17p (Mackay <I>et al., </I>1988a). Following on from this work the incidence of LOH in primary breast tumours was determined at other loci on chromosome 17p and served a two fold purpose. First, the pattern of LOH at different loci on chromosome 17 in individual breast tumours was determined in order to define a shortest region of overlap (SRO). Identification of such a region, commonly lost in all tumours showing LOH, could be used to pinpoint the position of the putative tumour suppressor gene. Secondly, as two of the probes used to investigate LOH detect loci close to the known tumour suppressor gene p53, a potential role of the p53 gene in breast cancer development could be investigated. Two tumour samples showed LOH at the p53 locus and not at the more distal 17p13.3 site, suggesting the involvement of the p53 gene in breast tumorigenesis. Furthermore LOH at the p53 gene locus was detected in 49% of primary breast tumour samples. Exons 5-9 of the p53 gene, which contain known mutation hotspots, were examined for mutation in 78 primary breast tumours using the HOT (amplification and mismatch detection) technique. Twenty four (31%) of the breast tumours were found to possess a somatically acquired p52 mutation, mostly single base substitutions resulting in missense mutations. In tumours with data on both LOH and p53 mutation, the majority of p53 mutations were found to be accompanied by LOH, indicating the importance of the removal of the tumour suppressive function of the gene.