HIGH-INCIDENCE OF LOSS OF HETEROZYGOSITY AT CHROMOSOME 17P13 IN BREAST-TUMORS FROM BRCA2 MUTATION CARRIERS

Breast tumours from BRCA1 and BRCA2 mutation carriers are genetically instable and display specific patterns of chromosomal aberrations, sug gestive of distinct genetic pathways in tumour progression, The freque ncy of abnormalities affecting chromosome 17p and the TP53 gene was de termined in 27 breast tumours from 26 female patients carrying the Ice landic BRCA2 founder mutation (999del5), Loss of heterozygosity (LOH) was detected in 23 of the 27 tumours (85%), The majority of tumours ma nifesting LOH had lost a large region on 17p, although a more restrict ed loss, including the TP53 locus was seen in a few tumours. Positive p53 immunostaining was observed in 18 of 26 tumours (69%), However, mu tations in the TP53 gene were detected in only three tumours (11%), in cluding a missense (codon 139) and a nonsense mutation (codon 306) in two tumours with moderate p53 expression and a frameshift deletion (co don 182) in a tumour with no detectable p53 expression, Positive p53 i mmunostaining, mainly weak, was observed in 16 of the 24 tumours (66%) without TP53 mutation, The high frequency of LOH at chromosome 17p13 suggests that one or more genes from this region are involved in the d evelopment of BRCA2-induced breast cancer. The frequent finding of wea k overexpression of, presumably wild type p53 protein, suggests an alt ernative mechanism of TP53 involvement specific to these tumours.