Loss of heterozygosity and tumor suppressor gene mutations in chondrosarcomas.

Loss of heterozygosity (LOH) of chromosomes 13q and 17p and mutations of the retinoblastoma (Rb) and p53 gene were studied in 28 tumors from 22 patients with chondrosarcomas. Allele loss at polymorphic loci on 13q was found in 36% of tumors and the frequency was much higher in grade II (56%) or high grade (40%) tumors than in grade I tumors (18%). LOH of 17p, which was detected in 25% of all tumors, was of low frequency in low grade tumors (8% in grade I and 20% in grade II), whereas 80% of tumors with high grade tumors were positive for LOH. These observations may imply that LOH on 13q and 17p contributes to the tumor development at different stages. In low grade cases (grade I and II), tumor recurrence was observed more frequently in primary tumors with LOH on 13q (86%) than those without (8%), suggesting the significance of LOH analysis in the assessment of biological behavior of tumors. Structural alteration of the Rb gene was found in one dedifferentiated tumor, and point mutations of the p53 gene were found in all of five high grade tumors, indicating that high grade chondrosarcomas were genetically equivalent to other high grade sarcomas such as osteosarcomas.