144 Abstracts

TUMOR SPECIFIC DIMINUTION OF CHROMOSOMAL TELOMERES K. Holzmann I , W. Henn I , G. Seitz 2, C. Welter 1 , N. Blin 1 1 Inst. of Human Genetics & 2pathology, Univ. of the Saar 6650 Homburg/Saar, Germany

Tumor cells display genomic instabilities in comparison to their healthy counterparts. For better understanding of structural aberrations and to obtain a more detailed picture of the DNA changes within the chromosomes we investigated the repeats of chromosomal termini in different renal tumors and corresponding healthy tissues. When the genomic DNA was analyzed by several restriction enzymes (EcoRI, Sail, BamHI, Hpall, Mspl) and probed with an oligonucleotide (TTAGGG)3, the results were not very conclusive. When Hinfl and Alul were used, a reduction in size and quantity was notable in the tumor DNA. Most strikingly, the two tumor samples with the most extensive telomeric losses showed, by cytogenetic analysis, telomeric fusions; tumors with less pronounced reduction of the TTAGGG-repeat displayed no telomeric fusions. Thus, the terminal instabilities seem to precede the end-to- end chromosome fusions and this phenomenon could play a role in genetic instability leading to tumorigenesis.

HETEROGENEITY IN BLADDER CANCER AS DETECTED BY CHROMOSOME ANALYSIS AND INTERPHASE CYTOGENETICS. ~ . ~ . _ ~ , , ~ 1 , AHN Hopman 2, RFM Schapers 3, RPE Pauwels 3, FCS Ramaekers 2. Hosp. pharmacy and laboratory Venray (1), Dept. mol. cell biol. genetics, Univ. Limburg (2), Hosp. Venlo-Venray (3). The Netherlands.

The presence of hyperdiploid cells amongst predominantly diploid ones is an indication for increased chance of progression of bladder cancer. As a result counting of chromosomes can be very informative. We examined 30 bladder cancers by means of flow- cytometry (FCM) to detect the DNA index (D.I), by counting the number of metaphases with 2n, 3n, 4n, >-5n chromosomes and by in situ hybridization (ISH) using centromere specific probes counted in 200 cells, for chromosomes 1,7,9,11. Of 21 tumours, staged Ta or T1, having a DI of 1, in 14 cases low percentages of 4n or 3n cells were detected. The modal number of chromosomes (m.n.)was 2n. With ISH in 8 cases a low percentage of cells showed multiple copies for each of the probes, indicating tetraploidization. In 13 cases an imbalance between different chromosomes was seen. Of 9 tumours, staged T1 to T3, having a DI between 1.6 and 1.9, the m.n. was 3n. In 4 cases cells >=5n were found and in 5 other cases 2n cells were present. Using ISH in all cases aneuploidy was detected as well as chromosome imbalances. In 8 cases a low percentage of cells with multiple copies of the main fractions was detected, indicating polyploidization. In conclusion we can state that tetraploidization, a generally accepted concept for tumour progression, is much more frequently detected by chromosome counting than with ISH. If we take into account the heterogeneity on the basis of individual chromosomes, ISH enables us to detect this phenomenon routinely. Using FCM no indication for tetraploidization, c.q.progression was obtained.