No abstract

The present data provide further indications that increased MDM2 expression level, caused by gene amplification or altered regulation of transcription, is involved in tumor progression of some, but not all, sarcoma subtypes.

Extra abnormal chromosomes (rings and giant rods) containing chromosome 12 sequences are characteristic of well-differentiated liposarcoma (WDLPS). By whole chromosome painting we found in 6 WDLPS that minimally 5 chromosomes had contributed to the formation of the extra abnormal chromosomes. To the constant chromosome 12 contribution, sequences were variably added from chromosomes 1, 4, and 16. Material from chromosomes 1, 4, and 12 was identified by painting in interphase nuclear projections ("blebs") and in micronuclei consistent with the concept that blebs are precursors to micronuclei. The complexity of the mechanisms generating the extra abnormal chromosomes in WDLPS was also attested to by the diversity and, in some cases, intricacy of the patterns of fluorescence. To begin to fathom the function of the extra abnormal chromosomes we examined the amplification of genes, including SAS, MDM2, and GADD153/CHOP, known to be in the region 12q13-14. SAS and MDM2 demonstrated constant co-amplification. GADD153/CHOP, which is critically rearranged in myxoid liposarcoma, was not amplified in WDLPS.

Using comparative genomic hybridization (CGH), we have identified and mapped regions of DNA amplification in primary and metastatic osteosarcomas. Samples were obtained from four patients and ten independent xenografts. Sixty‐four percent of the tumors showed increased DNA‐sequence copy numbers, affecting 23 different chromosomal sites. Most of these regions were not previously associated with the development and/or progression of these tumors. Amplicons originating from 1q21–q23, 6p, 8q23‐qter, and 17p11‐p12 were observed most frequently. The 6p and 17p11–p12 amplicons seem to be specific for osteosarcomas, indicating that these regions may harbor genes relevant for the development of these tumors.