Loss of heterozygosity at BRCA1, TP53, nm-23 and other loci on chromosome 17q in human breast carcinoma.

BACKGROUND In Egypt, breast cancer ranks number one among the female malignancies. Activation of oncogenes and inactivation of tumor suppressor genes are thought to play an important role in the development and progression of breast cancer. PURPOSE The present study is a trial to investigate the role of chromosome 17 in sporadic invasive ductal carcinoma of the breast through detection of LOH for 6 highly polymorphic microsatellite loci, two of which are located at BRCA1 gene (D17S855 and D17S856), one at TP53 gene, one at nm-23 gene and finally two at 17q12-12.3 (D17S183 and D17S250). MATERIAL AND METHODS Tissue samples and their corresponding safety margin normal tissues were collected from 25 patients with invasive ductal carcinoma of the breast of grades 2 and 3. LOH was detected for the 6 highly polymorphic microsatellite markers mentioned previously using PCR assay. RESULTS The percentage of overall LOH recorded was 68% of the cases examined. The highest LOH recorded in D17S855 and D17S856 (43% and 32% respectively), both markers are located at BRCA1 gene, followed by 32% LOH in nm-23 gene. D17S183 and D17S250, which are localised telomeric and centromeric to BRCA1 gene, showed 24% and 28% LOH, respectively. The lowest percentage of LOH was observed in the TP53 gene (14%). No significant correlation was found between each of the six markers used and lymph node status, grade, or menopausal status. LOH at the nm-23 marker exhibited a significant association with lymph node involvement. CONCLUSION It can be concluded from the present study that BRCA1 gene may be involved in carcinogenesis of some sporadic breast cancer cases. Deletion in nm-23 gene is associated with advanced stage of the disease. Finally, another gene located at 17q12-12.3 region may be involved in some sporadic breast cancer cases.