HIGH-INCIDENCE OF LOSS OF HETEROZYGOSITY IN BREAST-TUMORS FROM CARRIERS OF THE BRCA2 999DEL5 MUTATION

Germ-line mutation in the BRCA2 gene confers an increased risk of brea st cancer. An elevation of additional genetic defects in tumors of pat ients with germ-line mutation in the BRCA2 gene compared with sporadic breast tumors has been reported, To evaluate the nature of the differ ence, we did detailed mapping of chromosomes 1p, 3p, 6q, 11, 13q, 16q, 17, and 20q, using microsatellite markers. We found that the frequenc y of loss of heterozygosity was similar at some chromosomal regions in the BRCA2 999del5 and sporadic tumors but significantly different at others, These others include chromosomal arms 3p, 6q, 11p, 11q, 13q, a nd 17p. Loss of heterozygosity mapping suggests that the same chromoso me regions are involved in both tumor groups but at elevated frequenci es in BRCA2 999del5 tumors, This higher frequency of genetic aberratio ns could pinpoint genes that selectively promote tumor progression in individuals predisposed to breast cancer due to the BRCA2 999del5 germ -line mutation. Accumulation of somatic genetic changes during tumor p rogression may follow a specific and more aggressive pathway of chromo some damage in these individuals.