ArticleFrontiers in oncology2014
Evidence That GRIN2A Mutations in Melanoma Correlate with Decreased Survival.
Article in Frontiers in oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Computational Identification of Novel Stage-Specific Biomarkers in Colorectal Cancer Progression.PloS one · 2016Pooled it
- Biomarker Analyses Investigating Disease Biology and Associations with Outcomes in the JAVELIN Merkel 200 Trial of Avelumab in Metastatic Merkel Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Peripheral Blood Gene Expression and Protein Profiles of Purinergic and Glutamatergic Signaling Components and PD-L1 in Gastric Cancer: A Cross-Sectional Study.Current issues in molecular biology · 2026Article
- Assessment of 1863International journal of molecular sciences · 2025Article
- Spitz melanoma with MAP3K8::ABLIM1 rearrangement: a case report with review of the literature.Diagnostic pathology · 2024Review
- Metastatic extraneural glioblastoma diagnosed with molecular testing.The oncologist · 2024Article
- Undifferentiated and Dedifferentiated Metastatic Melanomas Masquerading as Soft Tissue Sarcomas: Mutational Signature Analysis and Immunotherapy Response.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2023Article
- Neuronal Cannabinoid CBCancers · 2023Article
- NMDA Receptor and Its Emerging Role in Cancer.International journal of molecular sciences · 2023Review
- Small RNA sequencing and identification of papaya (Carica papaya L.) miRNAs with potential cross-kingdom human gene targets.Molecular genetics and genomics : MGG · 2022Article
- The Dark Side of Melanin Secretion in Cutaneous Melanoma Aggressiveness.Frontiers in oncology · 2022Review
- Review
- Review
- Highly expressed Claudin18.2 as a potential therapeutic target in advanced gastric signet-ring cell carcinoma (SRCC).Journal of gastrointestinal oncology · 2020Article
- Discovery and validation of methylated-differentially expressed genes in Helicobacter pylori-induced gastric cancer.Cancer gene therapy · 2020Article
- Association Between Parkinson's Disease and Melanoma: Putting the Pieces Together.Frontiers in aging neuroscience · 2020Article
- Unchecked immunity: a unique case of sequential immune-related adverse events with Pembrolizumab.Journal for immunotherapy of cancer · 2019Article
- NR1 and NR3B Composed IntranuclearInternational journal of molecular sciences · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous whole-exome sequencing has demonstrated that melanoma tumors harbor mutations in the GRIN2A gene. GRIN2A encodes the regulatory GluN2A subunit of the glutamate-gated N-methyl-d-aspartate receptor (NMDAR), involvement of which in melanoma remains undefined. Here, we sequenced coding exons of GRIN2A in 19 low-passage melanoma cell lines derived from patients with metastatic melanoma. Potential mutation impact was evaluated in silico, including within the GluN2A crystal structure, and clinical correlations were sought. We found that of 19 metastatic melanoma tumors, four (21%) carried five missense mutations in the evolutionarily conserved domains of GRIN2A; two were previously reported. Melanoma cells that carried these mutations were treatment-naïve. Sorting intolerant from tolerant analysis predicted that S349F, G762E, and P1132L would disrupt protein function. When modeled into the crystal structure of GluN2A, G762E was seen to potentially alter GluN1-GluN2A interactions and ligand binding, implying disruption to NMDAR functionality. Patients whose tumors carried non-synonymous GRIN2A mutations had faster disease progression and shorter overall survival (P < 0.05). This was in contrast to the BRAF V600E mutation, found in 58% of tumors but showing no correlation with clinical outcome (P = 0.963). Although numbers of patients in this study are small, and firm conclusions about the association between GRIN2A mutations and poor clinical outcome cannot be drawn, our results highlight the high prevalence of GRIN2A mutations in metastatic melanoma and suggest for the first time that mutated NMDARs impact melanoma progression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.