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.
Thus, BLBC progression is promoted by increasing activities of wild-type N-Ras, which mediates autocrine/paracrine signaling that can influence both cancer and stroma cells.
However, melanoma-specific survival was significantly poorer for higher-risk (T2b or higher stage) tumors with NRAS (2.9 [1.1-7.7]) or BRAF (3.1 [1.2-8.5]) mutations (P = .04) but not for lower-risk (T2a or lower) tumors with NRAS (0.9 [0.3-3.0]) or BRAF (0.6 [0.2-1.7]) (P = .65), as adjusted for age, sex, site, AJCC tumor stage, TIL grade, and study center.
Until recently, there has been a paucity of promising genetically targeted therapy approaches for NRAS-mutant melanoma (and RAS-mutant malignancies in general).
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.
NRAS(G12V) maintained leukemia self-renewal through mTOR and MEK pathway activation, implicating these pathways as potential targets for cancer stem cell-specific therapies.
Clinical and pathologic data were collected retrospectively on melanoma patients tested for B-RAF and N-RAS mutations at the Yale Cancer Center and associations with survival were determined.
In fact, it is able to oppose various steps of tumor progression when overexpressed in cell lines by influencing invasion, survival to anoikis, extravasation, lung metastasis formation, and chemotherapy response. miR-148b controls malignancy by coordinating a novel pathway involving over 130 genes and, in particular, it directly targets players of the integrin signaling, such as ITGA5, ROCK1, PIK3CA/p110α, and NRAS, as well as CSF1, a growth factor for stroma cells.
To our knowledge, MEK162 is the first targeted therapy to show activity in patients with NRAS -mutated melanoma and might offer a new option for a cancer with few effective treatments.
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.
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.
By a multivariate analysis, fine needle aspiration biopsy cytology classification, the presence of a NRAS mutation, and the tissue inhibitor of metalloproteinase 1 expression level were associated jointly with malignancy.
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.
The p21 RAS subfamily of small GTPases, including KRAS, HRAS, and NRAS, regulates cell proliferation, cytoskeletal organization, and other signaling networks, and is the most frequent target of activating mutations in 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.
In this paper, we review data of recent literature on the distribution in centenarians of germ-line polymorphisms, which are supposed to affect the individual susceptibility to cancer (p53, HRAS1, BRCA1, glutathione transferases, cytochrome oxidases, steroid-5 alpha-reductase enzyme type II).