Hereditary suppression of lethal (2) giant larvae malignant tumor development in Drosophila by gene transfer

Abstract

Homozygous mutations of the recessive oncogene lethal-(2) giant larvae (l(2)gl) of Drosophila melanogaster cause lethal neoplasms of the imaginal discs and the brain hemisphere. A 13-kb DNA segment spanning the l(2)gl+ locus has been inserted into P element vectors and used for P-mediated transformation. The P-l(2)gl+ transposons have been introduced into the germ line of heterozygous l(2)gl-/+ flies and were shown by backcrossing to fully rescue the homozygous l(2)gl deficient animals, which otherwise would have died of brain and imaginal disc neoplasms. Further genetic backcrossing with l(2)gl deficiencies characterized by deletions of increased sizes involving the left end of chromosome 2 indicated that a relatively large region of developmentally regulated DNA sequence adjacent to the l(2)gl gene is apparently not essential for the viability and fertility of the fly. These experiments indicate that all the genetic information specified by the l(2)gl+ gene is contained within this 13-kb DNA segment and demonstrates that the development of neuroblastomas and imaginal disc tumors results from the absence of l(2)gl function. When this function is restored, tumor development is completely suppressed.