N2/M2 lesions are characterized by inflammatory-type and AXL gene signatures with an equal distribution of wild-type and mutated BRAF and low prevalence of NRAS mutations in M2 melanomas.
This study investigated the utility of protein expression phenotyping to provide an integrated assessment of gene expression programs in BRAF/NRASmelanoma which would be useful for prognosis and may predict response to MEK inhibition.
In this study, we identify a novel cytoplasmic intergenic lincRNA (MIRAT), which is upregulated following prolonged MAPK inhibition in NRAS mutant melanoma and modulates MAPK signaling by binding to the MEK scaffold protein IQGAP1.
PLA2G6 rs132985*T was associated with BRAF V600E (OR = 1.32, 95% CI = 1.05-1.67) and BRAF other (OR = 1.82, 95% CI = 1.11-2.98), but not BRAF V600K or NRAS+ melanoma.
Combining 6-thio-dG with the mitochondrial inhibitor Gamitrinib attenuated this adaptive response and more effectively suppressed NRAS-mutant melanoma.
We compared the rapid, real-time, fully automated molecular diagnosis platform Idylla™ with next-generation sequencing (NGS) and immunohistochemistry for detection of BRAF and NRAS mutations in 36 patients with metastatic melanomas.
The rarity of HRAS and KRAS Q61R mutants in malignant melanoma let previous investigations erroneously conclude that SP174 is specific for NRASQ61R-mutant protein.
These representative cases suggest that comprehensive BRAF/NRAS ctDNA monitoring during anti-PD1 therapy is informative and can be of added value for the monitoring of melanoma patients gaining clinical benefit on anti-PD1 treatment.
The etiology and pathogenesis of the pediatric melanoma is currently being investigated; studies have examined the genetic alterations that may be involved with the development of pediatric melanomas including TERT promoter, BRAF, and NRAS among others.
Considering the antitumor activity of benzothiazolic derivatives, this study aimed to demonstrate the action of benzothiazolic (E)-2-((2-(benzo[d]thiazol-2-yl)hydrazono)methyl)-4-nitrophenol (AFN01) against three established human melanoma cell lines that recapitulate the molecular landscape of the disease in terms of its genetic alterations and mutations, such as the TP53, NRAS and B-RAF genes.
Leptomeningeal melanocytes are more susceptible to transformation by oncogenic NRAS than cutaneous melanocytes, and central nervous system melanomas are more common than cutaneous melanomas in the setting of CMN.
Knock down of Beclin1 or of ATG5 prevented neratinib and neratinib combined with sodium valproate / AR42 from reducing the expression of mutant N-RAS in established PDX and fresh PDX models of ovarian cancer and melanoma, respectively.
There was poor agreement for both BRAF and NRAS mutation status between incident and subsequent melanomas (κ = 0.10, 95% CI -0.10 to 0.42; κ = 0.06, 95% CI -0.10 to 0.57, respectively).
Therapy with oral MEK inhibitors before or after checkpoint inhibitor therapy showed a trend toward a survival benefit in patients with NRAS mutant melanoma.
Cohorts B and C: patients with BRAF- or NRAS-mutant melanoma who had either undergone surgical resection of high-risk disease (cohort B) or were receiving or had received medical therapy for advanced disease (cohort C).
This explorative biomarker study examined circulating BRAF and NRAS mutations in a cohort of 125 patients with melanoma receiving PD-1 antibodies alone or in combination with ipilimumab between July 3, 2014, and May 24, 2016.
This study utilizes an <i>in vivo</i> reporter model to optimize schedules and supports targeting mTORC1/2 to overcome MEKi plus CDK4/6i resistance.<b>Significance:</b> Mutant BRAF and NRASmelanomas acquire resistance to combined MEK and CDK4/6 inhibition via upregulation of mTOR pathway signaling.
Somewhat distinct from sun exposure-related human cutaneous melanomas, there is growing evidence that a variety of gene copy number alterations and protein structure/function mutations play roles in canine melanomas, in circumstances more analogous to human mucosal melanomas and to some extent other melanomas with murine sarcoma viral oncogene homolog B (<i>BRAF</i>), Neuroblastoma RAS Viral (V-Ras) Oncogene Homolog (<i>NRAS</i>), and neurofibromin 1 tumor suppressor <i>NF1</i> triple wild-type genotype.
We conclude that the combination of trametinib and GSK2141795 does not have significant clinical activity in NRAS-mutant or BRAF<sup>WT</sup> NRAS<sup>WT</sup> melanoma.