GOK - A GENE AT 11P15 INVOLVED IN RHABDOMYOSARCOMA AND RHABDOID TUMOR-DEVELOPMENT

The expression of GOK, a gene recently identified at 11p15.5, was stud ied in breast cancer, rhabdomyosarcoma, and rhabdoid tumor cell lines. In these neoplasms, deletions at 11p15 and suppression of tumorigenic ity induced by a normal human chromosome 11 were previously demonstrat ed, Whereas breast cancer cell lines express readily detectable levels of GOK mRNA, expression is absent in rhabdomyosarcoma and rhabdoid tu mor cell lines, This is in contrast with the high expression of GOK in skeletal muscle, the normal tissue of origin of rhabdomyosarcomas, su ggesting that down-regulation of GOK expression could be involved in t umor development, In agreement with this hypothesis, transfection of G OK cDNA into G401 derived from a rhabdoid tumor and RD cells derived f rom a rhabdomyosarcoma that do not express detectable levels of GOK mR NA, induced cell death, Because GOK expression is not compatible with growth of these tumor cells, these results support the hypothesis that loss of GOK expression plays a role in tumor establishment or progres sion and suggest that GOK may act as a recessive tumor suppressor gene in rhabdomyosarcomas and rhabdoid tumors, On the contrary, transfecti on of GOK cDNA into the breast cancer cell line HBL100 produced no det ectable effects, indicating that the growth-suppressive effect of GOK in RD and G401 cells was specific. Because rhabdomyosarcomas have been observed in cases of Beckwith-Wiedemann syndrome, a genetic disorder linked to 11p15, a role of GOK in this disease cannot be excluded.