CHROMOSOMAL ORGANIZATION OF AMPLIFIED CHROMOSOME-12 SEQUENCES IN MESENCHYMAL TUMORS-DETECTED BY FLUORESCENCE IN-SITU HYBRIDIZATION

The chromosomal organization of amplified chromosome 12 sequences was studied with fluorescence in situ hybridization in six mesenchymal tum ors: two osteosarcomas, one lipoma, two liposarcomas, and one fibrosar coma. All except the fibrosarcoma contained ring and/or giant marker c hromosomes. Amplification of chromosome 12 sequences, demonstrated wit h whole-chromosome paint in all cases, was confined to ring and giant marker chromosomes in four tumors. In one of the osteosarcomas and in the fibrosarcoma, amplified sequences were added to chromosome 12 and to chromosomes 10, 12, 18, and the Y chromosome, respectively. Hybridi zations with single-copy probes demonstrated considerable inter- and i ntracellular variation in the arrangement of chromosome 12 sequences i n ring and marker chromosomes. Amplification of 12q13-15 sequences, pr edominantly from the HMGIC-MDM2 region, was detected in all cases, but the two osteosarcomas also contained amplification of 12p material. T his finding, combined with results from previous studies, indicates th at 12p amplification is a feature distinguishing osteosarcomas from ad ipose tissue tumors. A novel finding was the presence of positive sign als for chromosome 12 alpha-satellite sequences in ring and marker chr omosomes in four cases. Rod chromosomes carrying amplified material, i n particular those that were relatively stable, frequently exhibited c hromosome 12 negative terminal segments; two of these, present in two separate cases, were shown by C-banding to contain constitutive hetero chromatin. The significant intercellular heterogeneity in the number a nd structure of rings and giant markers in a subset of mesenchymal tum ors could be explained by continuous recombination through breakage-fu sion-bridge cycles. If so, this process will continue until broken end s become stabilized, for example by acquisition of telomeric segments from other chromosomes. Genes Chromosomes Cancer 23:203-212, 1998. (C) 1998 Wiley-Liss, Inc.