ArticleOncogene2015
SETD2 loss-of-function promotes renal cancer branched evolution through replication stress and impaired DNA repair.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed, 176 citations in OpenAlex.
- Somatic mutational landscape in von Hippel-Lindau familial hemangioblastoma.Molecular oncology · 2026Article
- BAP1 deficiency-induced SKA3 promotes clear cell renal cell carcinoma malignant progression by regulating chromosomal instability.Cell death & disease · 2026Article
- MSL2 disruption leads to autism-like behaviors, impairs neurogenesis, and alters histone H4K16 acetylation.Cellular and molecular life sciences : CMLS · 2026Article
- The H3K36me3 methyltransferase SETD2 contributes to PAF1C interactions with RNA Pol II and is required for neuronal differentiation.The EMBO journal · 2026Article
- Emerging roles for the epigenetic modifiers PBRM1 SETD2 and BAP1 in clear cell renal cell carcinoma pathogenesis and prognosis beyond VHL.Discover oncology · 2026Review
- Article
- Daxx-Dependent H3.3 Deposition Promotes Double-Strand Breaks Repair by Homologous Recombination.Cells · 2026Article
- The cGAS-STING pathway in cancer immunotherapy: prognostic value and therapeutic potential.Frontiers in immunology · 2026Review
- Prognostic Role of Global DNA Methylation in Renal Cancer Reveals Decitabine Treatment Benefit.Current medicinal chemistry · 2026Article
- Identification of Predictive Genomic Biomarkers in Metastatic Clear Cell Renal Cell Carcinoma: A Comprehensive Analysis of Real-World Clinicogenomic Data.JCO precision oncology · 2026Article
- Loss of SETD2 in wild-type VHL clear cell renal cell carcinoma sensitizes cells to STF-62247 and leads to DNA damage, cell cycle arrest, and cell death characteristic of pyroptosis.Molecular oncology · 2025Article
- SETD2 loss of function is a recurrent event in advanced-phase chronic myeloid leukemia and contributes to genomic instability: SETD2 loss in Chronic Myeloid Leukemia.Clinical and translational medicine · 2025Article
- K-Means Clustering of HyperpolarisedCancers · 2025Article
- A new insight into the impact of copy number variations on cell cycle deregulation of luminal-type breast cancer.Oncology reviews · 2025Review
- Review
- Multi-omic and single-cell profiling of chromothriptic medulloblastoma reveals genomic and transcriptomic consequences of genome instability.Nature communications · 2024Article
- Catalytic activity of Setd2 is essential for embryonic development in mice: establishment of a mouse model harboring patient-derived Setd2 mutation.Frontiers of medicine · 2024Article
- Prognostic and therapeutic roles ofAging · 2024Article
- The histone methyltransferase SETD2 regulates HIV expression and latency.PLoS pathogens · 2024Article
- VRK1 Regulates Sensitivity to Oxidative Stress by Altering Histone Epigenetic Modifications and the Nuclear Phosphoproteome in Tumor Cells.International journal of molecular sciences · 2024Article
50 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 9 institutions in 4 countries.
Funding
Abstract
Defining mechanisms that generate intratumour heterogeneity and branched evolution may inspire novel therapeutic approaches to limit tumour diversity and adaptation. SETD2 (Su(var), Enhancer of zeste, Trithorax-domain containing 2) trimethylates histone-3 lysine-36 (H3K36me3) at sites of active transcription and is mutated in diverse tumour types, including clear cell renal carcinomas (ccRCCs). Distinct SETD2 mutations have been identified in spatially separated regions in ccRCC, indicative of intratumour heterogeneity. In this study, we have addressed the consequences of SETD2 loss-of-function through an integrated bioinformatics and functional genomics approach. We find that bi-allelic SETD2 aberrations are not associated with microsatellite instability in ccRCC. SETD2 depletion in ccRCC cells revealed aberrant and reduced nucleosome compaction and chromatin association of the key replication proteins minichromosome maintenance complex component (MCM7) and DNA polymerase δ hindering replication fork progression, and failure to load lens epithelium-derived growth factor and the Rad51 homologous recombination repair factor at DNA breaks. Consistent with these data, we observe chromosomal breakpoint locations are biased away from H3K36me3 sites in SETD2 wild-type ccRCCs relative to tumours with bi-allelic SETD2 aberrations and that H3K36me3-negative ccRCCs display elevated DNA damage in vivo. These data suggest a role for SETD2 in maintaining genome integrity through nucleosome stabilization, suppression of replication stress and the coordination of DNA repair.
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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.