Chromosome 8p alterations in sporadic and BRCA2 999del5 linked breast cancer

Chromosomal losses involving the short arm of chromosome 8 are frequent in a variety of tumour types, including breast cancer, suggesting the presence of one or more tumour suppressor genes in this region. In this study, we h ave used 11 microsatellite markers to analyse loss of heterozygosity (LOH) at chromosome 8p in 151 sporadic breast tumours and 50 tumours from subject s carrying the BRCA2 999del5 mutation. Fifty percent of sporadic tumours co mpared to 78% of BRCA2 linked tumours exhibit LOH at one or more markers at 8p showing that chromosome 8p alterations in breast tumours from BRCA2 999 del5 carriers are more pronounced than in sporadic breast tumours. The patt ern of LOH is different in the two groups and a higher proportion of BRCA2 tumours have LOH in a large region of chromosome 8p. In the total patient m aterial, LOH of 8p is associated with LOH at other chromosome regions, for example, 1p, 3p, 6q, 7q, 9p, 11p, 13q, 17p, and 20q, but no association is found between LOH at 8p and chromosome regions 11q, 16q, 17q, and 18q. Furt hermore, an association is detected between LOH at 8p and positive node sta tus, large tumour size, aneuploidy, and high S phase fraction. Breast cance r patients with LOH at chromosome 8p have a worse prognosis than patients w ithout this defect. Multivariate analysis suggests that LOH at 8p is an ind ependent prognostic factor. We conclude that chromosome 8p carries a tumour suppressor gene or genes, the loss of which results in growth advantage of breast tumour cells, especially in carriers of the BRCA2 999del5 mutation.