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.
Our results suggest that the combination of BRAF and NRAS mutation analysis with fusion gene detection contributes to diagnosis of malignant melanoma and clear cell sarcoma, and that insulin-like growth factor 1R might be a novel target for the treatment of these two malignancies.
The HRAS1 variable number of tandem repeats (VNTR) polymorphism, 1 kb downstream from the HRAS1 gene, has been reported to be associated with risk of various cancers.
In the present study, the mutational profile of the Tet methylcytosine dioxygenase 2 (TET2), the isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2), the serine/arginine-rich splicing factor 2 (SRSF2), the splicing factor 3b subunit 1 (SF3B1), the Kirsten rat sarcoma viral oncogene homolog (KRAS) and the neuroblastoma RAS viral oncogene homolog (NRAS), commonly mutated in human myeloid malignancies and mastocytosis, was investigated in canine MCTs.
These results indicate the following: (i) RAS oncogenes are not found in all types of human malignancies, (ii) significant differences in the frequency of RAS mutations can be found among subtypes of neoplasms derived from the same tissue, (iii) in lymphoid neoplasms the NRAS mutation correlates with the most undifferentiated acute lymphocytic leukemia phenotype, and (iv) NRAS mutations present in only a fraction of malignant cells may result from either the selective loss or the acquisition of mutated alleles during tumor development.
The Idylla NRAS-BRAF mutation test has been developed for the qualitative detection of mutations in <i>NRAS</i> and <i>BRAF</i> oncogenes, facilitating genetic profiling of patients with cancer.
Two hundred sixty-two evaluable, primary, high-risk stage I (grade 3, or aneuploid grade 1 or 2, or clear cell) and stage II-IV EOCs, collected at the University Hospitals Leuven and within the European Organisation for Research and Treatment of Cancer 55971 trial, were genotyped for hotspot mutations in KRAS (COSMIC [Catalogue of Somatic Mutations in Cancer] coverage >97%), BRAF (>94%), NRAS (>97%), PIK3CA (>79%), PTEN, FBXW7 (>57%), AKT2, AKT3, and FOXL2, using Sequenom MassARRAY.
Both the present case-control study (odds ratio, 1.83; 95 percent confidence interval, 1.28 to 2.67; P = 0.002) and the present study combined with our previous study (odds ratio, 2.07; 95 percent confidence interval, 1.47 to 2.92; P < 0.001), as well as the meta-analysis of all 23 studies (odds ratio, 1.93; 95 percent confidence interval, 1.63 to 2.30; chi-square = 57.58; P < 0.001), replicated our original finding and demonstrated a significant association of rare HRAS1 alleles with cancer.
Mutations in the three closely related RAS genes, HRAS, KRAS, and NRAS are among the most common mutations found in human cancer; reaching 50% in some types of cancer, such as colorectal carcinoma, and 10% in prostate cancers.
Somatic mutations in the small GTPase NRAS are the most common activating lesions found in human cancer and are generally associated with poor response to standard therapies.
Additionally, the specific p.G12RNRAS mutation in this case is a common somatic mutation in cancer cells, and analysis of previously reported NRAS-RASopathy cases suggests that mutations at traditionally oncogenic codons are associated with elevated cancer risk not present with mutations at other sites.
However, there are also commoner genes conferring lower risks but accounting for a more substantial fraction of cancer cases; those so far identified include the ataxia-telangiectasia gene and the HRAS1 minisatellite locus.
NRAS(G12V) maintained leukemia self-renewal through mTOR and MEK pathway activation, implicating these pathways as potential targets for cancer stem cell-specific therapies.
With this report, we expand the genotype and phenotype spectrum of RASopathy-associated germline NRAS variants and provide evidence that NRAS variants do not spare the cancer-associated mutation hotspots.
Our study demonstrates the protective role of keratinocytic RxRα in (1) suppressing spontaneous and acute UVB-induced melanoma, and (2) preventing progression of the melanoma to malignancy in the presence of driver mutations like activated CDK4 <sup>R24C/R24C</sup> and oncogenic NRAS <sup>Q61K</sup> .