A region close to Tp53 shows LOH in familial breast cancer

The proportions of mutation of BRCA1 and BRCA2 detected in familial breast cancer vary in different regions. Most breast cancer families in Sweden cannot be explained by mutations in the known major susceptibility genes. Our previous studies have found a high frequency of LOH in the Tp53 region in familial breast cancer suggesting a putative tumor suppressor gene in this region, and the Tp53 gene was excluded as predisposing gene in these families by mutation screening. In order to identify other candidate tumor suppressor genes responsible for familial breast cancer, we performed LOH analysis in 98 paired tumor and blood samples from 91 breast cancer families using 11 microsatellite markers on chromosome 17p. Two loci with high frequency of LOH were found. One spanned the Tp53 gene, the other was distal to Tp53. Linkage studies were performed on 17p with 11 microsatellite markers in 102 breast cancer families with no detectable mutations in the BRCA1 and BRCA2 gene. The linkage analysis did not further support any of the regions suggested by the LOH study. However, since the Tp53 gene is already known to predispose to breast cancer as well as being involved in tumor progression, it is possible that also this region, close but distal to Tp53 contains a gene involved in familial and/or sporadic breast cancer development similar to Tp53.