ArticleNature genetics2012
Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma.
Article in Nature genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 688 papers, 3 of them syntheses that pooled it.
What it found
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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
688 citing papers in PubMed, 3 syntheses or guidelines pooled it, 1,178 citations in OpenAlex.
- Management of Uveal Melanoma: Updated Cancer Care Alberta Clinical Practice Guideline.Current oncology (Toronto, Ont.) · 2023Guideline
- Systematic review and meta-analysis of genomic alterations in acral melanoma.Pigment cell & melanoma research · 2022Pooled it
- Integrated genomic analysis identifies a genetic mutation model predicting response to immune checkpoint inhibitors in melanoma.Cancer medicine · 2020Pooled it
- Atezolizumab plus Bevacizumab in Patients with Unresectable or Metastatic Mucosal Melanoma: A Multicenter, Open-Label, Single-Arm Phase II Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- RAC1 signaling in polyploid giant cancer cells: Implications for tumorigenesis and therapy resistance.Cancer letters · 2026Review
- GTP biosynthesis is a therapeutic vulnerability in Rac1-mutant melanoma.bioRxiv : the preprint server for biology · 2026Article
- Genetic Drivers of Sensitivity or Resistance to RAS(ON) Multiselective Inhibitors in NRAS-Mutated Melanoma.Cancer research · 2026Article
- Alternative Splicing of a Structured Partner Alters the Folding-Upon-Binding Trajectory of an Intrinsically Disordered Protein.Journal of the American Chemical Society · 2026Article
- A Phase II Trial of Defactinib Combined with Avutometinib in Patients with Metastatic Uveal Melanoma.Cancers · 2026Article
- Preclinical and Virtual Models of Mucosal Melanoma: Bridging Translational Gaps in a Rare and Lethal Cancer.Pigment cell & melanoma research · 2026Review
- Article
- Genetic landscape of stage II melanoma identifies CBL as a new driver gene and prognostic biomarker.British journal of cancer · 2026Article
- Recent advances in the molecular genetic mechanisms and immune microenvironment of uveal melanoma.Melanoma research · 2026Review
- Rho GTPases in cancer resistance: mechanisms, vulnerabilities, and therapeutic opportunities.Biochemical Society transactions · 2026Review
- Genomic, Clinical, and Spatial Predictors of Durable Response to BRAF/MEK Inhibition inbioRxiv : the preprint server for biology · 2026Article
- Article
- The cytokinesis regulator RacGAP1 is a Rac1-specific GAP on membranes.Protein science : a publication of the Protein Society · 2026Article
- An evolutionarily conserved salt bridge stabilizes the active site for GTP hydrolysis in Rho GTPases.The Journal of biological chemistry · 2026Article
- RHOA at the intersection of inflammation-driven and sporadic colorectal cancer.Frontiers in immunology · 2026Review
- A critical role of FAK signaling in Rac1-driven melanoma cell resistance to MAPK pathway inhibition.Oncogene · 2025Article
628 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors at 5 institutions in 2 countries.
Funding
Abstract
We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1(P29S)) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1(P29S) showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.
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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.