1/3. Molecular genetic characterization of both components of a dedifferentiated chondrosarcoma, with implications for its histogenesis. Dedifferentiated chondrosarcoma is defined as a high-grade, anaplastic sarcoma adjacent to a low-grade malignant cartilage-forming tumour. Controversy remains as to whether the anaplastic and cartilaginous components are derived from a common precursor cell, or whether they represent separate genotypic lineages (collision tumour). Both components of a case of dedifferentiated chondrosarcoma were therefore separately investigated by loss of heterozygosity (LOH) analysis, comparative genomic hybridization (CGH), dna flow cytometry, and p53 analysis. Both showed p53 overexpression and an identical somatic 6 bp deletion in exon 7 of p53. Combination of the CGH and LOH results revealed that both components had lost the same copy of chromosome 13. These results provide compelling evidence in this case for a common origin, instead of the 'collision tumour' theory. Certain genotypic alterations were not shared. The anaplastic component showed severe aneuploidy, LOH at additional loci, and amplification and deletion of several chromosome parts. In contrast, the cartilaginous component had lost chromosomes 5, 22, 17p and part of 16p and revealed an amplification of 17q. The LOH and CGH results further demonstrated that the two components had lost a different copy of chromosome 4. Thus, a substantial number of genetic alterations have occurred after the diversion of the two components, indicating that the separation of the two clones, derived from a single precursor, was a relatively early event in the histogenesis of this case of dedifferentiated chondrosarcoma. ( info) |