Activated ras genes in human seminoma: evidence for tumor heterogeneity.

The incidence of mutations in cellular ras genes was determined in human seminoma, a germ cell tumor of the testis, with the aid of specific oligonucleotide probe hybridization. To eliminate the large number of nonneoplastic cells present in seminomas, aneuploid tumor cell nuclei were isolated from the tumor tissue by flow sorting. Mutations were detected in 40% of the seminomas at codons 12 or 61 of either the Ki-ras or the N-ras gene. No correlation was found with histopathological or clinical features. In some seminomas the mutant gene was present in only a fraction of the tumor cell population, suggesting tumor heterogeneity for ras gene mutations. Yet, flow cytometric measurement of nuclear DNA contents and histological examination of tumor tissue did not reveal two different tumor cell populations. We conclude from these observations that ras mutation is probably not the initial genetic event in the development of seminoma.