GROWTH, METASTASIS, AND INVASIVENESS OF DROSOPHILA TUMORS CAUSED BY MUTATIONS IN SPECIFIC TUMOR-SUPPRESSOR GENES

More than 50 genes have been identified in Drosophila by loss-of-funct ion mutations that lead to overgrowth of specific tissues. Loss-of-fun ction mutations in the lethal giant larvae, discs large, or brain tumo r genes cause neoplastic overgrowth of larval brains and imaginal disc s. In the present study, the growth and metastatic potential of tumors resulting from mutations in these genes were quantified. Overgrown br ains and imaginal discs were transplanted into adults and beta-galacto sidase accumulation was used as a marker to identify donor cells. Muta tions in these three genes generated tumors with similar metastatic pa tterns. For brain tumors, the metastatic index (a measure we defined a s the fraction of hosts that acquired secondary tumors normalized for the amount of primary tumor growth) of each of the three mutants was s imilar. Analysis of cell proliferation in mutant brains suggests that the tumors arise from a population of several hundred cells which repr esent only 1-2% of the cells in third instar larval brains. For imagin al disc tumors from lethal giant larvae and brain tumor mutants, it is shown for the first time that they can be metastatic and invasive. Pr imary imaginal disc tumors from lethal giant lan,ae and brain tu,nor m utants formed secondary tumors in 43 and 53% of the hosts, respective ly, although the secondary tumors were, in general, smaller than the s econdary tumors derived from primary brain tumors.