HUMAN CHROMOSOME-11 CONTAINS 2 DIFFERENT GROWTH SUPPRESSOR GENES FOR EMBRYONAL RHABDOMYOSARCOMA

The identification of acquired homozygosity in human cancers implies locations of tumor suppressor genes without providing functional evidence. The localization of a defect in embryonal rhabdomyosarcomas to chromosomal region 11p15 provides one such example. In this report, we show that transfer of a normal human chromosome 11 into an embryonal rhabdomyosarcoma cell line elicited a dramatic loss of the proliferative capacity of the transferrants. Indeed, the majority of the viable microcell hybrids had either eliminated genetic information on the short arm of the transferred chromosome 11 or increased the copy number of the rhabdomyosarcoma-derived chromosomes 11. Cells that possessed only the long arm of chromosome 11 also demonstrated a decreased growth rate. In contrast, all microcell hybrids retained the ability to form tumors upon inoculation into animals. These functional data support molecular studies indicating loss of genetic information on chromosome 11p15 during the development of embryonal rhabdomyosarcoma. In addition, our studies demonstrate the existence of a second gene on the long arm, previously unrecognized by molecular analyses, which negatively regulates the growth of embryonal rhabdomyosarcoma cell lines.