CORRELATION OF CYTOGENETIC AND FLUORESCENCE IN-SITU HYBRIDIZATION (FISH) STUDIES IN NORMAL AND GLIOTIC BRAIN

In vitro, tissue culturing, for karyotype analysis, may introduce arti facts confounding the cytogenetic evaluation of tissues with low basel ine proliferative activity. Utilizing a panel of fluorescence in situ hybridization (FISH) probes for chromosomes 7, 8, 9, 10, 12, 17, 18, X , and Y, we compared the results of FISH analysis of non-tumorous norm al (11 patients) and gliotic (10 patients) brain tissue touch preparat ions with those of cytogenetic evaluation performed on shortterm prima ry cultures of the same material. We found a significant rate of appar ent monosomy of chromosomes 8 and 17 by FISH analysis, with no corresp onding clonal chromosomal loss detected by karyotype evaluation. These monosomy rates were significantly lower in gliotic than in normal bra in tissue, and image anlaysis suggested that this apparent monosomy wa s due to interphase pairing of homologous centromere signals. Two dist inct Y-chromosome signals were seen in 9.4% of nuclei by FISH, with 3 of 15 males displaying disomy Y rates over 15%. Disomy Y rates correla ted approximately with age and clonal disomy Y was seen in the karyoty pe of one of these specimens. Karyotype analysis demonstrated loss of a sex chromosome in 6 specimens, while no sex chromosome nullisomy was detected by FISH. FISH is a valuable adjunct to the cytogenetic evalu ation of tissues with low baseline proliferative activity. The differe nces in relatiave monosomy rates between normal and gliotic brain sugg est that alterations in nuclear architecture and/or DNA sequence accom pany the transition from normal to reactive glia.