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    GENE:

    SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

    i
    Other names: SETD2, SET Domain Containing 2, Histone Lysine Methyltransferase, HIF-1, KMT3A, HYPB, Histone-Lysine N-Methyltransferase SETD2, Protein-Lysine N-Methyltransferase SETD2, Huntingtin-Interacting Protein B, Lysine N-Methyltransferase 3A, Huntingtin Yeast Partner B, SET Domain Containing 2, KIAA1732, P231HBP, HIP-1, SET2, Huntingtin Interacting Protein 1, Huntingtin-Interacting Protein 1, SET Domain-Containing Protein 2, FLJ23184, HSPC069, HBP231, SETD2, HSET2, HIF1, LLS
    12d
    Case Report: Mixed ductal-lobular carcinoma consisting of invasive lobular carcinoma with a glycogen-rich clear cell pattern and elevated tumor mutation burden. (PubMed, Front Oncol)
    This experience also shows that SETD2 functional impairment may underlie gILC hypermutation, while HNF1B overexpression could contributes to a glycogen-rich clear cytoplasm. Overall, this case emphasizes the complexity of MDL with gILC, and highlights the need for further studies to clarify the underlying molecular mechanisms and their prognostic implications.
    Journal • Tumor mutational burden
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    ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • SMAD4 (SMAD family member 4) • CDH1 (Cadherin 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)
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    ER positive • PIK3CA mutation
    15d
    The SETD2 L1609P mutation found in leukemia disrupts methyltransferase activity and reduces histone H3K36 trimethylation. (PubMed, J Biol Chem)
    These findings support the pivotal role of SETD2 inactivation and subsequent disruption of H3K36me3 deposition in oncogenesis, particularly in hematologic malignancies. Our study provides the first mechanistic and three-dimensional protein structure information on how SETD2-associated cancer mutations can lead to altered H3K36 methyltransferase activity.
    Journal
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    SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)
    17d
    Chromosome 3p deletion leads to extensive genomic alterations in diverse cancers and confers synthetic lethality in uveal melanoma. (PubMed, bioRxiv)
    We further show that MITF, MYC, and GNAQ/GNA11 form coupled regulatory feedback loops in the melanocyte lineage, and MITF deletion in UVM creates acute dependency on MYC-mediated rescue via chr8q amplification, often as a consequence of isochromosome formation. The discovered feedback loops predict both overall and relapse-free patient survival within the most aggressive UVM subtype, explain sensitivity to therapeutic gene perturbations, and inform effective combinatorial therapies.
    Journal
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    TP53 (Tumor protein P53) • GNAQ (G Protein Subunit Alpha Q) • GNA11 (G Protein Subunit Alpha 11) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • MITF (Melanocyte Inducing Transcription Factor)
    17d
    Clinicopathological and molecular features of acquired cystic disease-associated renal cell carcinoma (PubMed, Zhonghua Bing Li Xue Za Zhi)
    ACD-RCC is a rare renal cell carcinoma that occurs in patients with end-stage renal disease and has unique morphological features. It is often associated with favorable prognosis and alterations in genes related to the MTOR/TSC pathway or chromatin modification.
    Journal
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    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • KMT2C (Lysine Methyltransferase 2C) • TSC2 (TSC complex subunit 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • TSC1 (TSC complex subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • TFE3 (Transcription Factor Binding To IGHM Enhancer 3) • MME (Membrane Metalloendopeptidase) • KMT2B (Lysine Methyltransferase 2B) • GATA3 (GATA binding protein 3) • PAX8 (Paired box 8) • TFEB (Transcription Factor EB 2)
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    TP53 mutation
    26d
    The fall of the genome protectors triad: PBRM1, SETD2, and BAP1's impact on metabolism and immunity in clear cell renal cell carcinoma. (PubMed, Front Cell Dev Biol)
    Although emerging studies are beginning to provide insight, evidence suggests roles for PBRM1, SETD2, and BAP1 in metabolic regulation and in shaping the tumor immune microenvironment in ccRCC. Here, we review recent advances in this field and examine their impact on the management of ccRCC.
    Review • Journal • BRCA Biomarker • IO biomarker
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    CD8 (cluster of differentiation 8) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)
    28d
    Prognostic value of glioma-associated oncogene homolog 1 and SET domain-containing protein 2 immunohistochemical scores in locally advanced cervical cancer. (PubMed, Oncol Lett)
    The univariate analysis revealed that lower OS was associated with nGLI IS >6 [hazard ratio (HR), 1.50; 95% CI, 1.44-14.13; P=0.010] and ncGLI1 IS 6 (HR, 1.53; 95% CI, 1.23-17.49; P=0.023). The present study results demonstrated the utility of IS in evaluating the prognostic impact of SETD2 and GLI1 expression in patients with LACC.
    Journal
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    SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • GLI1 (GLI Family Zinc Finger 1)
    28d
    Prolonged survival in EGFR exon 20 insertion mutant lung adenocarcinoma: case report of sequential osimertinib and furmonertinib with research trend analysis. (PubMed, Front Med (Lausanne))
    This analysis demonstrated a growing global research focus on third-generation EGFR-TKIs and variant-specific treatment strategies for EGFR ex20ins-mutant NSCLC, supporting the rationale underpinning the therapeutic approach adopted in this report. Sequential high-dose third-generation EGFR-TKIs may offer clinically meaningful benefit in selected EGFR ex20ins cases; however, this strategy remains non-standard and should be regarded as hypothesis-generating, warranting further prospective evaluation.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • ETV6 (ETS Variant Transcription Factor 6) • SMAD4 (SMAD family member 4) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)
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    PD-L1 expression • TP53 mutation • EGFR mutation • EGFR exon 20 insertion • EGFR exon 20 mutation
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    Tagrisso (osimertinib) • Ivesa (firmonertinib) • simmitinib (SYHA1817)
    1m
    Identification of Predictive Genomic Biomarkers in Metastatic Clear Cell Renal Cell Carcinoma: A Comprehensive Analysis of Real-World Clinicogenomic Data. (PubMed, JCO Precis Oncol)
    These findings require prospective validation to confirm their clinical utility.
    Journal • Real-world evidence • IO biomarker
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    TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • MTAP (Methylthioadenosine Phosphorylase) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NF2 (Neurofibromin 2) • TSC1 (TSC complex subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • KDM5C (Lysine Demethylase 5C)
    1m
    Distinct Molecular and Prognostic Profiles of Left- and Right-Sided Colorectal Cancer Revealed by NGS Analysis: The Role of SMAD4 and SETD2 Mutations. (PubMed, Cancer Med)
    These findings reveal criticalmolecular and prognostic differences between LCC and RCC and highlight SMAD4 and SETD2 asimportant prognostic biomarkers, suggesting the potential value of location-and mutation-guided precision therapies in CRC.
    Retrospective data • Journal • Next-generation sequencing
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    BRAF (B-raf proto-oncogene) • ARID1A (AT-rich interaction domain 1A) • SMAD4 (SMAD family member 4) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • PRDM1 (PR/SET Domain 1) • PI3K (Phosphoinositide 3-kinases)
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    BRAF mutation • ARID1A mutation
    2ms
    Structural variation drives enhancer hijacking via 3D genome disruption in ccRCC. (PubMed, NPJ Digit Med)
    Furthermore, we developed a machine learning-based prognostic framework using enhancer hijacking signatures. Collectively, this work establishes a valuable resource for ccRCC research by elucidating how SVs and 3D genome reorganization collectively drive oncogenesis, and translates these findings into a clinically applicable prognostic tool.
    Journal
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    PBRM1 (Polybromo 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)
    2ms
    SETD2 inhibited T-cell acute lymphocytic leukemia invasion and infiltration by inhibiting the JAK/STAT pathway. (PubMed, Mol Cell Biochem)
    In vivo experiments further confirmed that silencing SETD2 decreased the body weight of mice and increased the infiltration of JURKAT cells in the liver, kidney, spleen, lung, and brain, while overexpression of SETD2 showed inhibitory effects. In conclusion, SETD2 played an important role in T-ALL by inhibiting the JAK/STAT pathway to inhibit T-ALL proliferation, invasion, and transfection.
    Journal
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    SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)
    2ms
    Case Report: Ivonescimab in EGFR-mutant lung cancer with baseline malignant pleural effusion and acquired complex resistance. (PubMed, Front Immunol)
    The patient eventually developed resistance to both first-line gefitinib and later almonertinib...He received ivonescimab monotherapy, achieving disease control for nearly 5 months before transitioning to ivonescimab plus pemetrexed with continued benefit and a manageable safety profile. This case illustrates the potential benefit of ivonescimab in patients with EGFR-mutant LUAD and baseline MPE who develop complex, non-canonical resistance to EGFR-TKIs. These findings support further clinical evaluation of ivonescimab in this poor-prognosis subgroup and highlight the importance of repeated molecular profiling in guiding treatment strategy.
    Journal • Pleural effusion • PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • RB1 (RB Transcriptional Corepressor 1) • PD-1 (Programmed cell death 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CHEK1 (Checkpoint kinase 1) • DNMT1 (DNA methyltransferase 1) • AKT2 (V-akt murine thymoma viral oncogene homolog 2)
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    PD-L1 expression • TP53 mutation • EGFR mutation • EGFR exon 19 deletion • MET amplification • EGFR T790M • CHEK1 mutation
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    gefitinib • pemetrexed • Ameile (aumolertinib) • Yidafan (ivonescimab)