CHROMOSOME IMBALANCE AT THE 3P14 REGION IN HUMAN BREAST-TUMORS - HIGH-FREQUENCY IN PATIENTS WITH INHERITED PREDISPOSITION DUE TO BRCA2

Our previous studies have indicated that genetic aberrations in the 3p 14 region are more frequent in malignant tumours from hereditary breas t cancer patients than sporadic breast cancers. The main purpose of th is study was to test if BRCA2 susceptibility alleles contribute to imb alance in the 3p14 region. We mapped allelic imbalance at 3p14 in tumo urs from Icelandic sisters affected with breast cancer using a set of 10 microsatellite markers 1233-D3S1217-D3S1261-D3S1296-D3S1210-D3S1284 -cen). The patients were of known carrier status with respect to the 9 99del5 mutation in BRC42 which is the most common cause of hereditary breast cancer in Iceland. Of 103 patients, 32 in the group were mutati on carriers. A high degree of imbalance was observed in tumours from B RCA2 mutation carriers, ranging from 44 to 88% for individual markers. This was significantly higher than the percentage of imbalance in tum ours from non-carriers, where the frequency ranged from 25 to 43%. In both groups, we noted elevated 3p14 imbalance in patients with bilater al disease. Allelic imbalance was most commonly observed near the mark er D3S1210 (3p14.1-p12) and the FHIT gene (3p21.1-p14.2) for both grou ps. We conclude that genomic aberrations in 3p14 are especially freque nt in tumours with BRCA2 gene defects, and suggest that this is caused by regional loss of chromosome stability rather than selection. (C) 1 998 Elsevier Science Ltd.