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[Detection of genetic alterations in sporadic breast tumors]
R K Schmutzler1, A Homann, E Bierhoff
1Universitäts-Frauenklinik, Bonn.
Objective:
Loss of heterozygosity (LOH) indicates the existence of tumor suppressor genes (TSG) in the affected chromosomal loci. In order to uncover the involvement of such genes, we analyzed LOH in different chromosomal regions of sporadic breast carcinomas.
Material And Method:
47 breast cancer patients were screened for LOH with microsatellite markers on 18 different loci. DNA fragments were amplified by PCR from tumor and reference tissue. The PCR products were run on 8% denaturing polyacrylamide gels and visualized by silver straining.
Results:
The following LOH-rates were found for the different loci: D6S497 (6p21, WAF-Region): 0%, D7S495: 9%, D7S522: 13%, D7S523: 22%, D11S488 (11q24-25): 38%, D13s321 and D13s765 (13q13-14, Rb-Region): 30% and 17%, D13S260 and D13S267 (13q12.3, BRCA2-Region): 28% both, D16S539 (16q22-24, E-Cadherin-Region): 35%, D17S5 (17p13.3): 17%, TP53 (17p13.1): 32% D17S250 (17q11-12): 22%, D17S855 (17q21 within the BRCA1 gene): 25%, D17S579 (17q21 telomer from BRCA1): 13%, D17S846 (centromere from BRCA1): 17%, 17q24 (SSTR 2): 9%, D22S684 (22q12, NF2-Region): 20%. Overall 66% of the tumors exhibited LOH. Lymphnode positive tumors showed significantly higher LOH rates than lymphnode negative tumors.
Conclusions:
Highest LOH-rates were found on chromosomes 11, 13, 16 and 17 indicative of relevant TSG's in the examined loci. In addition the findings indicate prognostic relevance of multiple LOH's in breast cancer.