Complex composition and co-amplification of SAS and MDM2 in ring and giant rod marker chromosomes in well-differentiated liposarcoma.

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.