Although NRAS and BRAF mutation frequency and RAS protein expression are low, BRAF protein expression was intense; probably, NRAS and BRAF mutations are independent events and alternative molecular mechanisms in the primary oral mucosal melanoma tumorigenesis.
Mutation in one of three RAS genes (i.e., HRAS, KRAS, and NRAS) leading to constitutive activation of RAS signaling pathways is considered a key oncogenic event in human carcinogenesis.
With respect to carcinogenesis mechanisms, RCC is associated with known gene types, such as MMR, KRAS, BRAF, and miRNA-31, while LCC is associated with CIN, p53, NRAS, miRNA-146a, miRNA-147b, and miRNA-1288.
Interestingly however, we recently found that loss of wild-type HRAS, NRAS, and even more potently, loss of both of these genes actually enhanced oncogenic KRAS-driven early tumorigenesis.
In many different human cancers, one of the HRAS, NRAS, or KRAS genes in the RAS family of small GTPases acquires an oncogenic mutation that renders the encoded protein constitutively GTP-bound and thereby active, which is well established to promote tumorigenesis.
Of note, collaboration of GAB2 with mutant NRAS enhanced tumorigenesis in vivo and led to an increased vessel density with strong CD34 and VEGFR2 activity.
The c-Met pathway is known to play a role in melanoma tumorigenesis and preliminary data from our laboratory suggested that this pathway is preferentially activated in NRAS-mutated tumors.
Activating mutations in members of the RAS oncogene family (KRAS, HRAS, and NRAS) have been found in a variety of human malignancies, suggesting a dominant role in carcinogenesis.
Apart from deregulation of the cell cycle and p53 pathway this finding indicates escape from replicative senescence (induced by mutated NRAS) and detachment-induced apoptosis as molecular mechanisms underlying the tumorigenesis of BON-1 cells.
Although N-ras gene mutation might be one of the mechanisms underlying oncogenesis of urothelial cancer, it seems to be a relatively rare event in Kasmiris, pointing to involvement of different etiological factors in the induction of bladder tumor in this population.
To determine which of these pathways are important for N-ras tumorigenesis in human cancer cells and also to investigate the possibility of cross talk among the pathways, we have utilized a human fibrosarcoma cell line (HT1080), which contains an endogenous mutated allele of the N-ras gene, and its derivative (MCH603c8), which lacks the mutant N-ras allele.
It is concluded that mutations in the Gs alpha gene (codons 159-240), the K- and N-ras genes (codons 1-71), the H-ras gene (codons 12/13) and mutations in the DNA-binding domain of the glucocorticoid receptor do not play a role in the tumorigenesis of canine corticotropic adenomas.
A similar genetic abnormality of N-ras genes at codon 61 between follicular adenoma and follicular carcinoma suggests that the mutation of N-ras at codon 61 might play a part in oncogenesis in follicular tumors.
Data concerning mutations of protooncogenes (H-, K-, and N-RAS) and tumor suppressor genes (retinoblastoma and p53 genes) in various common cancers are providing evidence of multiple genetic lesions that occur during the multistage process of carcinogenesis.
This report gives evidence that an amplified c-myc and a mutated N-ras gene are both present in this tumor cell line and provides support for the idea that co-operation of at least 2 activated cellular oncogenes is required for carcinogenesis.