Mutant c-K-ras genes were detected in about 75% of adenocarcinomas of the pancreas (n = 84); 40% of adenomas (n = 72) and carcinomas (n = 244) of the colon end rectum; 30% of carcinomas of the bile duct (n = 19); 25% of carcinomas of the lung (n = 92), and in lower frequency in other carcinomas, including liver, stomach, and kidney.
Paradoxically, reports have suggested a greater frequency of Ki-ras gene mutation in these lesions than in more complex lesions such as benign colonic adenomas and carcinomas.
None of the gastric and seven of the colorectal tumors had mutations of the c-K-ras gene. p53 gene mutations were detected in six gastric carcinomas [two out of 11 intramucosal carcinomas (18.2%) and four out of 11 invasive carcinomas (36.4%)].
The mutational frequency of the Ki-ras gene in the present series of small intestinal carcinomas was similar, while that of the p53 gene was slightly lower than the reported frequencies for colorectal carcinomas.
Combined Harvey rat sarcoma viral oncogene homolog/phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit α (HRAS/PIK3CA) mutations were observed predominantly in de novo carcinomas (5 of 8 vs 2 of 31 tumors; P = .035).
The findings for the Ki-ras gene in 42 paired carcinomas and synchronous metastases were identical, regardless of whether or not the carcinoma and its companion adenoma had identical Ki-ras findings.
RAS mutations in codon 61 were by far the most common genetic alteration in poorly differentiated carcinomas (23% of cases), with all mutation in NRAS except one in the HRAS gene.
K14/IL-1 alpha mice crossed with the highly sensitive TG.AC mice, constitutively expressing mutant Ha-Ras, also failed to develop papillomas or carcinomas.
Activating point mutations of genes of the RAS family (KRAS, HRAS and NRAS genes) are frequently found in carcinomas, but their prevalence in sarcomas varies considerably among ethnic groups.
Analysis of HK1.fos/alpha papillomas and carcinomas revealed that the endogenous c-Ha-ras gene possessed mutations at codons 12, 13, and 61 at the papilloma stage, but no mutations of the p53 tumor suppressor gene were detected.
The absence of ras mutations in the epithelium of primary oral squamous-cell carcinomas is of considerable interest as other work in our Department on Indian cases of oral carcinomas associated with chewing tobacco (quid) revealed that 35% of these had a codon 12, 13 or 61 mutation in Ha-ras.
Our results are the first demonstration of Ha-ras intron D alterations in human tumor tissues and suggest that concurrent mutations at codon 12 and intron D of this gene within the same tumor may contribute to the aggressive behavior of human bladder carcinomas.