Background: High frequencies of loss of heterozygosity (LOH) are found in familial breast carcinomas with BRCA mutations. Although LOH of BRCA1 does not coincide with somatic BRCA1 mutations, reduced BRCA1 protein expression and hypermethylation indicate the involvement of BRCA1 in sporadic carcinogenesis. To further investigate the role of BRCA we determined LOH of BRCA1 and correlated this with LOH in other breast cancer-associated regions.
Materials and methods: A total of 105 sporadic breast carcinomas were analysed for LOH in the regions of BRCA1, BRCA2, TP53, Caveolin1, "putative BRCA3", PTEN, ATM and E-cadherin and correlated it with clinicopathological features.
Results: We found an overall increase of LOH in carcinomas with simultaneous LOH of BRCA1. Significantly higher LOH rates were detected in the regions of TP53 (80%: 34.7%; p<0.005), 8q21 (72.7%: 30.6%; p<0.010) and 10q22-23 (21.1%: 5.9%; p=0.043). Moreover, estrogen receptor-negative carcinomas revealed LOH of BRCA1 more frequently than estrogen receptor-positive carcinomas (39%: 12%; p=0.003).
Conclusion: These data indicate that LOH of BRCA1 coincides with a defect of the DNA repair pathway. Therefore, LOH of BRCA1 determines a subgroup of sporadic breast carcinomas sharing genotype/phenotype features with familial breast carcinomas.