CLONING OF AN ACTIVATED HUMAN RET GENE WITH A NOVEL 5' SEQUENCE FUSED BY DNA REARRANGEMENT

By transfecting a high-M(r) DNA from human stomach cancer into NIH3T3 cells, a transforming sequence that showed homology with the human ret gene was identified. The transforming sequence was found to be generated by a DNA rearrangement in the human ret proto-oncogene. This rearrangement was suggested to have occurred during the transfection procedure. The nucleotide sequences of cDNAs of the rearranged ret gene and deduced amino acid (aa) sequences revealed that the rearrangement had resulted in recombination of the 3' segment of the ret proto-oncogene with a segment of an unknown human sequence, and that the recombination had generated a novel gene encoding a fusion protein of 435 aa. The rearrangement was presumed to be responsible for activation of the ret gene.