Genetic losses in breast cancer: toward an integrated molecular cytogenetic map

Breast cancer is the most common malignant disease in Caucasian women, but is less frequent in Chinese women. The molecular basis for such ethnical difference in disease pathogenesis remains unknown. To address this issue, we performed allelotyping analysis of formalin-fixed, paraffin-embedded samples from 21 Chinese patients with breast cancer using 59 fluorescently tagged oligonucleotide primers amplifying microsatellite loci. Loss of heterozygosity (LOH) was found in all tumor samples. Frequent allelic losses were identified at markers D3S1578 (56%); D7S507 (55%); D1S2766 (50%); D17S789 and D17S946 (43% each); D19S814 (35%); D2S162, D13S158 and D13S296 (33% each); D1S551 and D1S2800 (29% each); D3S1597 and D6S260 (22% each); and D1S1588 (21%). To compare our data to previous reports, we determined the band-specific frequency of chromosomal imbalances in breast cancer karyotypes reported in the Mitelman database, and from the CGH results of cases accessible through the Progenetix website. Furthermore, published LOH analyses of breast cancer cases were compared to our own LOH results, demonstrating the most common chromosomal regions affected by allelic losses. The combined results provide a comprehensive view of genetic losses in breast cancers, indicating the comparability of these different techniques and suggesting the presence of a distinct subset of breast cancers with high-frequency LOH at chromosomes 1 and 2p in Chinese patients.