Breast cancer in young women: prevalence of LOH at p53, BRCA1 and BRCA2

Full text

Previous studies have shown that breast cancers show more aggressive pathological features in younger women than those occurring in older women. These findings have raised the question whether differences are present at the molecular level. In order to examine genetic alterations associated with early onset breast cancer 31 cases, selected for age under 35 at diagnosis, were examined for loss of heterozygosity (LOH) and microsatellite instability (MI) in three key chromosomal intervals: 17p13 (p53), 17q11-22 (BRCA1) and 13q12-14 (BRCA2). The cases selected had no obvious family history. DNA was extracted from formalin-fixed paraffin embedded normal and tumour tissue (whole section and microdissected DNA) and analysed by PCR amplification of microsatellite repeat markers. Products were resolved on 10% non-denaturing polyacrylamide gels and silver stained.

28/31 (90%) cases exhibited LOH for at least one marker and 19 (61%) cases showed LOH at 2 or more markers. There was no MI detected. The frequency of LOH detected for each of the markers was as follows: 17p, D17S796 (37%) and D17S799 (61%); 17q, D17S855 (65%) and THRA1 (41%); and 13q, D13S171 (48%). These frequencies are higher (apart from THRA1) than those previously reported for unselected series of breast cancer. Other markers are currently being investigated. These results suggest that LOH at these regions could be related to early onset breast cancer and to poor tumour prognosis.