Patterns of allelic loss at the BRCA1 locus in Arabic women with breast cancer

Loss of heterozygosity (LOH) of BRCA1, a tumor suppressor gene, is one mech anism of genetic inactivation in both sporadic and familial forms of breast cancer. Studies reported in breast cancers from women of Northern European descent have shown LOH in 30-50% of sporadic tumors. Microsatellite instab ility (MSI) has served as evidence for involvement of DNA repair genes. Thi s study investigates the extent of allelic imbalance at the BRCA1 region in Arabic women with breast cancer. Paired normal and tumor tissue were avail able for DNA analysis in 13 cases. Results using fluorescent tagged primers to microsatellite markers D17S1323, D17S1325 and D17S855 intragenic to BRC A1 were analyzed using an ABI 310 DNA sequencer. As compared to normal DNA, MSI and LOH were recognized as a gain and a loss, respectively, of one sig nal in one allele in the tumor DNA. Microsatellite analyses showed 12 of 13 (92%) cases with LOH or MSI or both. Three cases demonstrated LOH alone, 3 cases with MSI alone. Six cases indicated both LOH and MSI; 2 cases with e ither LOH or MSI in separate markers. The combined finding of LOH and MSI i n the same marker was detected only with D17S1325 in 4/6 cases. The proport ion of aberrant findings of the BRCA1 locus in breast cancer appears to be higher in Arabic women than in other populations studied to date.