Primary mucosal melanomas represent a minority of melanomas, but have a significantly worse prognosis than cutaneous melanomas. A better characterization of the molecular pathogenesis of this melanoma subtype could help us understand the risk factors...
Mutations in NRAS constitutively activate cell proliferation signaling in malignant neoplasms, such as leukemia and melanoma, and the clarification of comprehensive downstream genes of NRAS might lead to the control of cell-proliferative signals of N...
Objective: To explore the influence of NRAS-AS on the proliferation, apoptosis, cell cycle, migration, and invasion ability of HCC cells, as well as its underlying mechanisms. Methods: A double-stranded cDNA library for liver cancer cells was constru...
(1) Background: NRAS mutations affect fewer than 1% of lung adenocarcinomas. The aim of this study was to describe the clinicopathological features of lung carcinomas with NRAS mutations. (2) Methods: A series of NRAS-mutated lung carcinomas was coll...
Melanoma patients carrying an oncogenic NRAS mutation represent 20% of all cases and present worse survival, relapse rate and therapy response than patients with wild type NRAS or with BRAF mutations. Nevertheless, no efficient targeted therapy has e...
26 September 2023
The aim of our study was to evaluate the incidence of KRAS/NRAS and BRAF mutations, analyze molecular patterns, and investigate associations with clinical parameters of these mutations in CRC KRAS/NRAS and BRAF mutations analyzed by next-generation s...
Background: Purely cutaneous Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder limited to the skin. To date, its pathogenesis remains unclear. Owing to recent findings of specific mutations in the mitogen-activated protein kina...
Background: The prognostic value of commonly recurrent mutations remains unclear in mucosal melanomas. Methods: Clinicopathologic parameters of 214 cases of mucosal melanomas diagnosed in 1989–2020 in several clinical institutions were analyzed. NRAS...
Mutations of the oncogenes v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and neuroblastoma RAS viral oncogene homolog (NRAS) are the most frequent genetic alterations in melanoma and are mutually exclusive. BRAF V600 mutations are predictive...
Hotspot mutations in the NRAS gene are causative genetic events associated with the development of melanoma. Currently, there are no FDA-approved drugs directly targeting NRAS mutations. Previously, we showed that p38 acts as a tumor suppressor in vi...
Purpose: To assess the efficiency of targeted radionuclide therapy (TRT), alone or in combination with MEK inhibitors (MEKi), in melanomas harboring constitutive MAPK/ERK activation responsible for tumor radioresistance. Methods: For TRT, we used a m...
Introduction: Patients with NRAS-mutant metastatic melanoma often have an aggressive disease requiring a fast-acting, effective therapy. The MEK inhibitor binimetinib shows an overall response rate of 15% in patients with NRAS-mutant melanoma, provid...
RAS oncogene family members are molecular switches of signaling pathways that control cell growth, proliferation, differentiation, and survival. In colorectal cancer, Kirsten-RAS (KRAS) and neuroblastoma-RAS (NRAS) are the commonly mutated isoforms....
This study aimed to analyze clinical and regional factors influencing the distribution of actionable genetic alterations in a large consecutive series of colorectal carcinomas (CRCs). KRAS, NRAS and BRAF mutations, HER2 amplification and overexpressi...
NRAS-mutant melanoma represents a clinically challenging subset of melanoma with limited effective therapies and intrinsic resistance to targeted MEK inhibition. Recent findings highlight protein S-nitrosylation, a redox-dependent post-translational...
Circulating tumour DNA (ctDNA) can be used to identify gene alterations. The purpose of this study was to determine whether the detection of ctDNA, based on the identification of BRAF and NRAS mutations before systemic treatment initiation, was assoc...
The high metastasis and mortality rates of melanoma in the era of chemotherapy have decreased significantly over the last 10 years. The success is owed largely to the introduction of targeted therapy of oncogenes and immunotherapies, such as checkpoi...
Background: Genetic variations, localized in the 3′ untranslated region (UTR) in mitogen-activated protein kinase (MAPK) pathway-related genes, may alter the transcription and impact the pathogenesis of laryngeal squamous cell carcinoma (LSCC). The p...
The diagnosis of endometrial cancer involves sequential, invasive tests to assess the thickness of the endometrium by a transvaginal ultrasound scan. In 6–33% of cases, endometrial biopsy results in inadequate tissue for a conclusive pathologic...
NRAS belongs to the RAS family of GTPases. In colorectal cancer (CRC), NRAS mutations are rare compared to KRAS, but may lead to worse outcomes. We report the functional characterization of the novel NRAS mutants—G48C, Q43K, and E37K—iden...
Advanced melanoma is a relentless tumor with a high metastatic potential. The combat of melanoma by using the targeted therapy is impeded because several major driver mutations fuel its growth (predominantly BRAF and NRAS). Both these mutated oncogen...
Background/Objectives: The clinical, histopathological, and dermoscopic features may be associated with melanoma mutational status. The aims of the study were to assess the clinical, histopathological, and dermoscopic features of melanoma to identify...
Vemurafenib is a BRAF (rapidly accelerated fibrosarcoma B-type)-targeted therapy used to treat patients with advanced, unresectable melanoma. It inhibits the MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinase) pathway...
Purpose: To assess the prognostic role of sentinel lymph node status (SLN) in melanoma patients, a statistical comparison was performed with the application of already known prognostic factors, mutational occurrence of BRAF and NRAS in the primary tu...
Histiocytoses encompass a group of exceptionally rare disorders characterized by the abnormal infiltration of tissues by histocytes. Among these, Erdheim–Chester disease (ECD) stands out as a multisystem histiocytosis that typically affects bon...
Aims: It is debated whether the NRAS-mutant melanoma is more aggressive than NRAS wildtype. It is equally controversial whether NRAS-mutant metastatic melanoma (MM) is more responsive to checkpoint inhibitor immunotherapy (CII). 331 patients treated...
The conformational changes in switch domains significantly affect the activity of NRAS. Gaussian-accelerated molecular dynamics (GaMD) simulations of three separate replicas were performed to decipher the effects of G13D, Q16R, and C118S on the confo...
Melanomas harboring NRAS mutations are a particularly aggressive and deadly subtype. If patients cannot tolerate or the melanomas are insensitive to immune checkpoint blockade, there are no effective 2nd-line treatment options. Drugs targeting the RA...
Slovakia has one of the highest rates of colorectal cancer among the developed countries, ranking as the second highest in the incidence of this disease for men worldwide. Despite the significant burden on both quality of life and the healthcare syst...
Background/Objective: Studies have shown an association between colorectal cancer (CRC) sidedness and gene mutations that may affect CRC clinical behavior. This study examined the association between specific KRAS, NRAS, and BRAF hot-spot mutations a...
Methods: We retrospectively and cross-sectionally reviewed the cases of 648 patients with a histological diagnosis of colon adenocarcinoma. Of these, 166 had partial molecular studies, and 42 cases were selected based on the availability of the genet...
Background/Objective: The prognostic value of specific hot-spot mutations within KRAS, NRAS, and BRAF genes in metastatic colorectal cancer (mCRC) genes remains debatable. This study explores whether certain KRAS, NRAS, and BRAF mutations are associa...
Australia’s housing affordability crisis has deepened despite extensive policy intervention, with the private rental sector experiencing unprecedented pressure. This study proposes that affordable housing should guarantee low and moderate-incom...
Malignant melanoma is a lethal skin cancer containing melanoma-initiating cells (MICs), implicated in tumorigenesis, invasion, and drug resistance, and characterized by an elevated expression of stem cell markers, including CD133. siRNA knockdown of...
Melanoma is the fifth most common cancer in the United States. The advent of immunotherapy and molecular targeted therapy has improved progression-free and overall survival in many patients with advanced disease. However, the selection of therapeutic...
TIGIT and its ligand CD155 (PVR) are emerging immune checkpoints in colorectal cancer (CRC), but their associations with mutational subtypes and the tumor immune milieu remain unclear. We quantified TIGIT and CD155 proteins by ELISA in paired CRC tum...
In this study, we investigated the expression of TIM-3 and Galectin-9 (Gal-9) in colorectal cancer (CRC) and their associations with oncogenic mutations, MSI status, cytokine profiles, and transcriptional data. TIM-3 and Gal-9 protein levels were sig...
Oncogenic Ras proteins are known to present multiple conformational states, as reported by the great variety of crystallographic structures. The GTP-bound states are grouped into two main states: the “inactive” state 1 and the “acti...
Background and objectives: Cancer represents the miscommunication between and within the body cells. The mutations of the oncogenes encoding the MAPK pathways play an important role in the development of tumoral diseases. The mutations of KRAS and BR...
Natural hematopoietic stem cells (HSC) are susceptible and tend to lose stemness, differentiate, or die on culture condition in vitro, which adds technical challenge for maintaining bona fide HSC-like cells, if ever generated, in protocol screening f...
The development of K-Ras independence may explain the failure of targeted therapy for pancreatic cancer (PC). In this paper, active N as well as K-Ras was shown in all human cell lines tested. In a cell line dependent on mutant K-Ras, it was shown th...
Acral naevi are benign melanocytic tumors occurring at acral sites. Occasionally they can progress to become malignant tumors (melanomas). The genetics of acral naevi have not been assessed in larger studies. In our study, a large cohort of 130 acral...
Melanocyte signaling through the MAPK pathway is orchestrated by NRas and relayed downstream via multiple effectors, such as RAF, Ral, and PI3K. In spite of their significance, the molecular mechanisms of signaling relay by NRas, their dynamics, and...
The coupling of alternative splicing with the nonsense-mediated decay (NMD) pathway maintains quality control of the transcriptome in eukaryotes by eliminating transcripts with premature termination codons (PTC) and fine-tunes gene expression. Long n...
In the Ptch+/- mouse model for embryonal rhabdomyosarcoma (ERMS), we recently showed that oncogenic (onc) H-, K- or NRAS mutations do not influence tumor growth when induced at the advanced, full-blown tumor stage. However, when induced at the invisi...
The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma; it is aberrantly activated in almost 80% of human cutaneous melanomas (≈50% BRAFV600 mutations and ≈30% NRAS mutations). While drugs targeting the MAPK pathway have...
Cyclin dependent kinase 11 (CDK11) is a protein kinase that regulates RNA transcription, pre-mRNA splicing, mitosis, and cell death. Targeting of CDK11 expression levels is effective in the experimental treatment of breast and other cancers, but thes...
Isolated from the marine bacteria Serinicoccus sp., seriniquinone (SQ1) has been characterized by its selective activity in melanoma cell lines marked by its modulation of human dermcidin and induction of autophagy and apoptosis. While an active lead...
In the present study, we employed the ddPCR and IHC techniques to assess the prevalence and roles of RAS and RAF mutations in a small batch of melanoma (n = 22), benign moles (n = 15), and normal skin samples (n = 15). Mutational screening revealed t...
Background/Objectives: Venous thromboembolism (VTE) is a common and clinically significant complication in patients with metastatic colorectal cancer (mCRC). Tumor sidedness and molecular alterations such as RAS and BRAF mutations are established pro...
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