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The transforming gene of malignant melanoma tissue obtained from a Japanese patient and maintained in nude mice has been cloned in its biologically active form and identified as the c-Ha-ras-1 gene, a homologue of the viral Ha-ras gene. Nucleotide sequence analysis revealed that the genetic alteration responsible for the transforming activity of the melanoma oncogene was localized to a single point mutation in the second exon. The transversion of adenine to thymine results in the substitution of leucine for glutamine as amino acid residue 61 of the predicted p21 protein. Other nucleotide sequences spanning a 2.9-kilobase segment including the entire exons and introns were found to be exactly the same as those in a proto-oncogene from a normal Caucasian reported previously, except for base alterations explained as polymorphic differences.

Molecular cloning and the total nucleotide sequence of the human c-Ha-ras-1 gene activated in a melanoma from a Japanese patient.