Using a probe that detects a polymorphic locus within the RB1 gene we found loss of only one allele (heterozygous deletion) in 33% of soft tissue sarcomas examined, including two leiomyosarcomas, a malignant peripheral nerve sheath tumour, a rhabdomyosarcoma and a chondrosarcoma.
In this study we analysed by immunohistochemistry the expression of p53 protein in 14 malignant fibrous histocytomas (MFHs), 22 other types of sarcoma (eight leiomyosarcomas, four rhabdomyosarcomas, four liposarcomas, two fibrosarcomas, two chondrosarcomas, one malignant schwannoma, and one dermatofibrosarcoma protuberans), and 25 non-malignant mesenchymal lesions (eight dermatofibromas, four cases of nodular fasciitis, three leiomyomas, three fibromatoses, two epithelioid.leiomyomas, two neurofibromas, one schwannoma, one myositis ossificans, and one giant cell tumour of tendon sheath).
These findings strongly suggest that p53 mutation plays a crucial role in the biologically aggressive subtype, and possibly in the process of tumor progression in human chondrosarcoma.
In chondrosarcomas, most of the p53-positive tumours belonged to highly malignant and atypical tumour types (dedifferentiated or mesenchymal type), suggesting a role for p53 mutation in the progression of cartilaginous tumours.
The overall arrangement of globular and carbohydrate-attachment domains is similar to human and rat chondrosarcomaaggrecan, but there are significant differences in detailed homology between chick and mammalian core proteins.
They include rearrangement of 8q12 in lipoblastomas, ring chromosomes in atypical lipomas, ring and giant marker chromosomes in well differentiated liposarcomas, t(12;16)(q13;p11) in myxoid liposarcomas, rearrangement of 7p21-22 in low-grade endometrial stromal sarcomas, t(2;13)(q37;q14) in alveolar rhabdomyosarcomas, t(X;18)(p11.2;q11.2) in synovial sarcomas, t(12;22) (q13;q13) in clear cell sarcomas, t(11;22)(q24;q12) in Ewing's sarcomas and peripheral neuroepitheliomas, and t(9;22)(q21-31;q11-12) in extraskeletal myxoid chondrosarcomas.
However, recent studies in sporadic and exostosis-derived chondrosarcomas suggest that the 8q24.1-encoded EXT1 gene may have tumour suppressor function.
These findings are consistent with previous cytogenetic reports of a recurrent t(9;22)(q22-31;q11-12) in the myxoid variant of chondrosarcoma and reveal involvement of the EWS gene in a fourth type of human sarcoma.
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.
In contrast, p53 gene mutations were detected at a lower frequency in malignant fibrous histiocytomas (2/34 cases) and not at all in nine chondrosarcomas and five leiomyosarcomas.