Chromosome imbalance at the 3p14 region in human breast tumours: high frequency in patients with inherited predisposition due to BRCA2.
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AuthorsBergthorsson, J T
Barkardottir, R B
MetadataShow full item record
CitationEur. J. Cancer. 1998, 34(1):142-7
AbstractOur previous studies have indicated that genetic aberrations in the 3p14 region are more frequent in malignant tumours from hereditary breast cancer patients than sporadic breast cancers. The main purpose of this study was to test if BRCA2 susceptibility alleles contribute to imbalance in the 3p14 region. We mapped allelic imbalance at 3p14 in tumours from Icelandic sisters affected with breast cancer using a set of 10 microsatellite markers (tel-D3S1295-D3S1234-D3S1300-D3S1600-D3S1233+ ++-D3S1217-D3S1261-D3S1296-D3S1210- D3S1284-cen). The patients were of known carrier status with respect to the 999del5 mutation in BRCA2 which is the most common cause of hereditary breast cancer in Iceland. Of 103 patients, 32 in the group were mutation carriers. A high degree of imbalance was observed in tumours from BRCA2 mutation carriers, ranging from 44 to 88% for individual markers. This was significantly higher than the percentage of imbalance in tumours from non-carriers, where the frequency ranged from 25 to 43%. In both groups, we noted elevated 3p14 imbalance in patients with bilateral disease. Allelic imbalance was most commonly observed near the marker D3S1210 (3p14.1-p12) and the FHIT gene (3p21.1-p14.2) for both groups. We conclude that genomic aberrations in 3p14 are especially frequent in tumours with BRCA2 gene defects, and suggest that this is caused by regional loss of chromosome stability rather than selection.
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