Alterations of mouse proto-oncogenes in sarcomas induced after transplantation of human tumors in athymic nude mice.
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During serial subcutaneous transplantation of several types of human tumors into nude mice, the local development of malignant mouse-specific sarcomas has been observed. Although the frequency of sarcoma induction is low, this phenomenon is very important because the mouse-specific sarcomas completely replaced the human tumors during serial transplantation. The DNA of five independently induced mouse-specific sarcomas was transfected into NIH/3T3 cells in order to detect oncogenes associated with mouse-specific sarcoma induction. Two of these DNAs were found to carry activated mouse c-N-ras and c-Ki-ras genes. The sequence analysis of the molecularly cloned mouse c-N-ras oncogene showed a single nucleotide transition from G to A at the 12th codon. This results in substitution of aspartic acid for glycine at this position. The mouse c-myc gene was also found to be amplified in a sarcoma. In these mouse sarcoma DNAs, human Alu sequences were not detected. These data strongly suggest that the mouse-specific sarcomas were not induced by the transfer of human transforming sequences but by the alterations of mouse proto-oncogenes.