Molecular diagnosis and gene therapy in musculoskeletal tumors

Significant progress has occurred in the molecular analyses of bone and soft-tissue tumors, and genetic studies have led to the development of important new diagnostic tools for the clinical management of patients with sarcomas. The detection of fusion genes induced by tumor-specific translocations, such as EWS-FLI1 in Ewing's sarcoma, SYT-SSX in synovial sarcoma, and CHOP-FUS in myxoid liposarcoma, is becoming significant for clinical diagnosis, because these sarcomas are often indistinguishable from other bone and soft-tissue tumors. Gene therapies with several gene transfer systems have been employed for some incurable cancers. It has been demonstrated that a Herpes simplex virus thymidine kinase (HSV-tk) gene can convert certain nucleoside analogs, such as ganciclovir, which disrupt DNA synthesis and are toxic to nucleosides. Human chondrosarcoma cells transduced with the HSV-tk gene were more sensitive to the cytotoxity of ganciclovir than non-transduced cells. Coculture of chondrosarcoma cells with and without the HSV-tk gene showed a bystander effect. The local injection of gene transduced cells into the chondrosarcoma implanted in nude mice markedly reduced tumor size after the administration of ganciclovir. These results suggested the possibility of gene therapy for chondrosarcoma.