GOK: A Gene at llplS Involved in Rhabdomyosarcoma and Rhabdoid Tumor Development1

The expression of GOK, a gene recently identified at llplS.5, was studied in breast cancer, rhabdomyosarcoma, and rhabdoid tumor cell lines. In these neoplasms, deletions at llplS and suppression of tumorigenicity induced by a normal human chromosome II were previously demonstrated. Whereas breast cancer cell lines express readily detectable levels of GOK mRNA, expression is absent in rhabdomyosarcoma and rhabdoid tumor cell lines. This is in contrast with the high expression of GOK in skeletal muscle, the normal tissue of origin of rhabdomyosarcomas, suggesting that down-regulation of GOK expression could be in volved in tumor development. In agreement with this hypothesis, transfection of GOK cDNA into G401 derived from a rhabdoid tumor and RD cells derived from a rhabdomyosarcoma that do not express detectable levels of GOK mRNA, 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 progression and suggest that GOK may act as a recessive tumor suppressor gene in rhabdomyosarcomas and rhabdoid tumors. On the contrary, transfection of GOK cDNA into the breast cancer cell line Ulti 10(1 produced no detectable effects, indicating that the growthsuppressive 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 1IplS, a role of GOK in this disease cannot be excluded.