Genetic alterations of chromosome 17 in human breast carcinoma studied by fluorescence in situ hybridization and molecular DNA techniques

Abstract Fluorescence in situ hybridization (FISH) with a chromosome 17 centromere-specific probe was used together with Southern blot analyses and PCR amplification of a polymorphic segment to characterize 13 breast carcinomas. Cells with an abnormal number of chromosome 17 centromeres were found mixed with disomic cells in nine of the 13 tumors studied. Three 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 alterations. In contrast, of the seven tumors found to have genetic alterations elsewhere on chromosome 17, all had more than one cell population when examined for numerical chromosome 17 alterations. The present data support the hypothesis that alterations at the distal short arm of chromosome 17 represent earlier events in the tumorigenic process than do the other chromosome 17 abnormalities observed. The results of molecular DNA studies interpreted as allelic imbalance of distal 17p markers in most cases probably reflect chromosomal rearrangements like loss of specific loci, rather than monosomies and large deletions. The report illustrates the usefulness of FISH when added to current molecular DNA techniques.