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.
C-myc and c-Ha-ras oncoprotein expression was studied by immunohistochemistry and gene detection by in situ hybridization on serial frozen sections of 32 breast lesions (19 benign biopsies and 13 infiltrating 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).
Different genes, located as the c-Ha-ras gene on the short arm of chromosome 11, were also found to be deleted suggesting that the deletion of other genes could play a role in aggressiveness of head and neck carcinomas.
Enhanced Ha-ras expression was documented in 66% of breast and 100% of colon carcinomas as compared with their normal counterparts, with levels in breast carcinomas ranging from 10.1 to 50.4 pg ras p21/micrograms protein and those in colon carcinomas ranging from 18.4 to 51.7 pg ras p21/micrograms protein.
Given the advantages of rat models characterized by larger organ size, abundant information regarding preneoplasias and virus-free constitution, we have concentrated on the generation of transgenic rats bearing copies of the human c-Ha-ras proto-oncogene and shown the Hras128 strain to be extremely sensitive to the induction of mammary carcinomas, and to a lesser extent, lesions in the urinary bladder, esophagus and skin.
If a mutation of c-K-ras 2 gene is an important component in the formation of adenocarcinoma, these results did not confirm the successive development from adenomas with severe atypia to advanced carcinomas as the main route for colorectal carcinogenesis in familial adenomatous polyposis patients.
Importantly, these studies also suggest for the first time that the distinct and likely cooperative biological functions of the Ki-ras-encoded Ki-Ras 4A and Ki-Ras 4B proteins may help explain why constitutively activating mutations of Ki-ras, but not N-ras or Ha-ras, are frequently detected in human carcinomas.
In contrast, no point mutation was detected in the 12th, 13th, and 61st codon of the c-Ki-ras and c-Ha-ras gene in 31 primary esophageal carcinomas including those from which TE1 and TE2 cell lines were established.
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.
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.
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%)].
Oncogenic HRAS Activates Epithelial-to-Mesenchymal Transition and Confers Stemness to p53-Deficient Urothelial Cells to Drive Muscle Invasion of Basal Subtype Carcinomas.
Our method of topographic genotyping of human colonic carcinomas has shown a correlation between K-ras-2 and p53 mutations and stage at diagnosis as well as long-term survival.