Analysis of the c‐myc, K‐ras and p53 Genes in Methylcholanthrene induced Mouse Sarcomas

We have examined 63 methylcholanthrene (MCA)‐induced mouse sarcomas for possible correlations of mutations involving the c‐myc, ras and p53 genes. The c‐myc gene was found to be amplified in 18 of these sarcomas (29%). Polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP) analysis and subsequent direct sequencing identified 18 cases carrying K‐ras mutation at codons 12, 13 and 61 (29%). No mutation was detected in the H‐ras and N‐ras genes. Mutations of the p53 gene in exons 5 to 8 were found in 45 cases (71%). Comparison of these mutations revealed that out of 18 cases with c‐myc gene amplifications, 10 carried K‐ras mutations (56%) and 14 carried p53 mutations (78%). In contrast, among 45 cases of sarcomas without c‐myc gene amplification, 8 were found to have K‐ras mutations (18%). The same 45 cases were found to have 31 p53 mutations (69%). The present study suggests a strong correlation between c‐myc gene amplification and K‐ras gene mutation (P < 0.01). p53 gene mutation was frequently found among MCA‐induced mouse sarcomas, indicating the importance of this mutation in the etiology of these tumors. However, p53 mutations were present in sarcomas regardless of the state of c‐myc amplification and K‐ras mutation. Therefore, a defect in the p53 gene is independent of amplification of the c‐myc gene or point mutation of the K‐ras gene.