Background: The authors' recent investigation of Korean patients with sarcoma has suggested that ras gene activation may play a role in oncogenesis. The authors attempted to extend the mutation analysis to sarcomas in American patients to determine whether there were racial or geographic factors relevant to the initiation or progression of sarcoma.
Methods: H-ras and K-ras genes were examined in sarcomas obtained from patients in the midwestern U. S. using the polymerase chain reaction technique and direct automated sequencing analysis. Tumors studied included 29 malignant fibrous histiocytomas, 7 liposarcomas, 5 rhabdomyosarcomas, and 9 leiomyosarcomas.
Results: Of the 50 sarcomas evaluated, only 1 (2%) definable mutation was found; a GGC to AGC transition at codon 12 of H-ras was found in a rhabdomyosarcoma. None of the patients had a K-ras mutation. The rates of incidence of ras point mutations in these samples were much lower (H-ras: 2%; 95% confidence interval [95% CI], 0-11.5% and K-ras: 0%) than described for both genes in Korean studies (H-ras: 16%; 95% CI, 5.2-26.8% and K-ras: 44%; 95% CI, 29.5-58.5%).
Conclusions: Although the reason for this discrepancy is not clear, there were no major differences found in histology or clinical stages. Based on this study of 50 sarcoma samples from American patients and the authors' previous study of 45 Korean tumor samples, the authors conclude that differing genetic and/or environmental mechanisms can affect sarcoma development or progression. Mutation of the H-ras and K-ras genes appears to be uncommon in sarcomas occurring in American patients, suggesting that the activation by point mutations of the H-ras and K-ras genes does not play a significant role in the pathogenesis or progression of sarcoma in these patients.