LINKAGE ANALYSIS AND ALLELIC IMBALANCE IN HUMAN BREAST-CANCER KINDREDS USING MICROSATELLITE MARKERS FROM THE SHORT ARM OF CHROMOSOME-3

Eight Icelandic breast cancer kindreds were subjected to linkage analy ses with respect to 28 microsatellite loci dispersed along the short a rm of chromosome 3. Breast tumors derived from these kindreds were con currently scored for allelic imbalance with ten of the markers. Linkag e to most markers could be excluded on the basis of negative LOD score s and haplotype analyses, although some moderately positive LOD scores resulted. A high frequency of imbalance in the familial tumors was se en with two of the markers in comparison with results obtained from sp oradic material. The highest frequency (68%) of imbalance was detected with the marker D3S1217, which is located on 3p14.2-p14.1. Imbalance at the D3S1211 locus, which is more telomeric (3p24.2-p22), was not si gnificantly elevated in the familial tumors. We suggest that the genet ic defect responsible for breast cancer susceptibility, in these famil ies either promotes instability in the 3p14.2-p14.1 region or enhances the selective advantage of such changes.