Alterations of mouse proto-oncogenes in sarcomas induced after transplantation of human tumors in athymic nude mice.

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.