GENETIC ALTERATIONS OF CHROMOSOME-17 IN HUMAN BREAST-CARCINOMA STUDIED BY FLUORESCENCE IN-SITU HYBRIDIZATION AND MOLECULAR DNA TECHNIQUES

Fluorescence in situ hybridization (FISH) with a chromosome 17 centrom ere-specific probe was used together with Southern blot analyses and P CR amplification of a polymorphic segment to characterize 13 breast ca rcinomas. Cells with an abnormal number of chromosome 17 centromeres w ere found mixed with disomic cells in nine of the 13 tumors studied. T hree of the four cases found to have a normal number of chromosome 17 centromeres had DNA alterations restricted to allelic imbalance of the two most distal markers on 17p; the fourth had no detectable alterati ons. In contrast, of the seven tumors found to have genetic alteration s elsewhere on chromosome 17, all had more than one cell population wh en examined for numerical chromosome 17 alterations. The present data support the hypothesis that alterations at the distal short arm of chr omosome 17 represent earlier events in the tumorigenic process than do the other chromosome 17 abnormalities observed. The results of molecu lar DNA studies interpreted as allelic imbalance of distal 17p markers in most cases probably reflect chromosomal rearrangements like loss o f specific loci, rather than monosomies and large deletions. The repor t illustrates the usefulness of FISH when added to current molecular D NA techniques.