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

Abstract

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.

Phyllodes tumors of the breast segregate in two groups according to genetic criteria

“…24 MDM2, a negative regulator of p53 was amplified in one of our phyllodes tumors cases. MDM2 is found to be frequently amplified in some sarcomas such as osteosarcomas, 46 liposarcomas, 47,48 'socalled' malignant histocytofibromas, 39,43 leiomyosarcomas 43 and neuroglial tumors. 49 The fact that in our This study has provided evidence that borderline and malignant phyllodes tumors could not be differentiated on the basis of the presence and of the number of chromosomal imbalances.…”

HMGIC, the gene for an architectural transcription factor, is amplified and rearranged in a subset of human sarcomas

“…WDLS are characterized by supernumerary abnormal chromosomes (rings or giant rod markers) containing sequences from the q13 ± 15 segment of chromosome 12 (Dal Cin et al, 1993). We have previously shown that MDM2, but not CDK4, is consistently included in amplicons in WDLS (Pedeutour et al, 1994). Sequences from several chromosomes contribute to these markers, making the generation of`secondary translocations' or of novel fusion genes within the markers likely.…”

Molecular cytogenetics of bone and soft tissue tumors

“…in other soft tissue tum ors, double m inutes, ring chrom osom es, an d large rod-shaped m arkers have repeatedly been en co u n tered. These latter anom alies appear to be associated w ith gene am plifications [6][7][8]. Also, osteosarcom as originate from supportive tissues [9].…”