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    GENE:

    POLE (DNA Polymerase Epsilon)

    i
    Other names: POLE1, DNA Polymerase Epsilon Catalytic Subunit, DNA Polymerase Epsilon Catalytic Subunit A, Polymerase (DNA) Epsilon Catalytic Subunit, DNA Polymerase II Subunit A, Polymerase (DNA Directed) Epsilon Catalytic Subunit, DNA Polymerase Epsilon Catalytic Subunit Protein, Polymerase (DNA Directed) Epsilon
    3d
    Correlation of Histopathological Parameters With Molecular Markers in Carcinoma Endometrium. (PubMed, Cureus)
    Immunohistochemical markers based on The Cancer Genome Atlas (TCGA) classification show a strong correlation with established histopathological risk factors. Integrating molecular profiling into the routine diagnostic workup may improve prognostication and support personalized treatment strategies in EC.
    Journal
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    POLE (DNA Polymerase Epsilon)
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    POLE mutation
    6d
    Distinct mutational landscape and clonal evolution of POLE-mutated endometrial cancer: geographic variation and insights into multiple classifier status. (PubMed, J Transl Med)
    This study refines the molecular landscape of POLEmut EC by demonstrating a potentially high prevalence of the V411L variant in the Chinese population and showing that the favorable prognosis of POLEmut EC remains largely consistent across different ethnic backgrounds and specific hotspot mutations in this real-world cohort. These findings support universal POLE testing to avoid overtreatment and provide a hypothesis-generating basis for large-scale, multi-center studies with longer follow-up to validate the distinct mutational spectrum across diverse Chinese regions and confirm the long-term prognostic stability of cases with multiple molecular classifiers.
    Journal • MSi-H Biomarker
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    TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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    TP53 mutation • MSI-H/dMMR • POLE mutation
    7d
    REPLACE: REal Word aPpLicAtion of Molecular Based Endometrial Cancer Classification (clinicaltrials.gov)
    P=N/A, N=264, Recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
    New trial
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    POLE (DNA Polymerase Epsilon)
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    POLE mutation
    8d
    Pole Walking Intervention in Retirement Communities (clinicaltrials.gov)
    P=N/A, N=53, Completed, University of Saskatchewan | Recruiting --> Completed
    Trial completion
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    POLE (DNA Polymerase Epsilon)
    10d
    A Study of Pembrolizumab and Olaparib in People With Endometrial Cancer or Endometrial Carcinosarcoma (clinicaltrials.gov)
    P2, N=26, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jan 2027 --> Apr 2026 | Trial primary completion date: Jan 2027 --> Apr 2026
    Trial completion • Trial completion date • Trial primary completion date
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    TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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    TP53 mutation • MSI-H/dMMR
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    Keytruda (pembrolizumab) • Lynparza (olaparib)
    10d
    Unusual Case of Neuromeningeal Late Relapse of POLE Mutated Endometrioid Carcinoma: A Case Report and Systematic Review. (PubMed, Curr Oncol)
    While POLE-mutated tumors overall retain an excellent prognosis, rare cases may follow an atypical and aggressive course. Improved molecular annotation and integrated risk-stratification models are needed to better identify this minority of higher-risk patients.
    Review • Journal
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    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • POLE (DNA Polymerase Epsilon)
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    TP53 mutation • TP53 wild-type • PTEN mutation • POLE mutation
    13d
    Copy Number-Low/TP53 Mutated Endometrial Cancer With Wild Type p53 Immunoexpression: Implications for Risk Stratification and Management When Using Next Generation Sequencing for Molecular Classification. (PubMed, Mod Pathol)
    Immunohistochemistry-based TCGA classification, such as the ProMisE protocol, will not be able to detect these cases as the p53 IHC pattern is wild type and there are no distinguishing morphological features; this may be of relevance for analyzing ProMisE protocol-based clinical trials and outcomes studies. Long term outcome studies are needed to refine risk stratification and treatment decisions for this unique molecular class of endometrial cancers that further contributes to the evolving understanding that the clinical significance of TP53 mutation in endometrial cancer is complex and depends on co-existing molecular alterations.
    Journal • Next-generation sequencing • P53WT
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    TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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    TP53 mutation • TP53 wild-type • POLE mutation
    14d
    A Study of Pembrolizumab and Olaparib in People With Endometrial Cancer or Endometrial Carcinosarcoma (clinicaltrials.gov)
    P2, N=26, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027
    Trial completion date • Trial primary completion date
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    TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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    TP53 mutation • MSI-H/dMMR
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    Keytruda (pembrolizumab) • Lynparza (olaparib)
    15d
    Immune checkpoint inhibitors in POLE/POLD1 proofreading-deficient CRC: from molecular basis to clinical practice and future directions. (PubMed, Immunotherapy)
    We highlight the critical need to distinguish passenger mutations from true proofreading defects, as therapeutic benefit is strictly tethered to functional pathogenicity. Finally, we propose an integrated biomarker framework that moves beyond binary genomic screening toward a functional hierarchy of polymerase variants, providing a definitive roadmap for the next generation of precision immunotherapy in colorectal cancer.
    Review • Journal • Checkpoint inhibition • Tumor mutational burden • MSi-H Biomarker • IO biomarker
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)
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    MSI-H/dMMR
    17d
    Toripalimab（JS001） as Monotherapy in Participants With POLE or POLD-1 Mutated and Non-MSI-H Advanced Solid Tumors (clinicaltrials.gov)
    P2, N=35, Recruiting, Sun Yat-sen University | Trial completion date: Jan 2024 --> Dec 2029 | Trial primary completion date: Jan 2024 --> Jan 2028
    Trial completion date • Trial primary completion date • Tumor mutational burden • IO biomarker • MSI-H
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    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)
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    POLE mutation • POLD1 mutation
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    Loqtorzi (toripalimab-tpzi)
    18d
    Cost and efficiency of universal versus selective next generation sequencing for advanced stage endometrial cancer. (PubMed, Gynecol Oncol)
    Selective molecular profiling of newly diagnosed stage III-IVA endometrial cancers using MMR and p53 IHC with reflex to NGS for p53-abnormal tumors improves testing efficiency and reduces unnecessary NGS compared with universal upfront NGS testing.
    Clinical • Journal • Next-generation sequencing
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    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)
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    TP53 mutation • POLE mutation
    24d
    NCI-2017-02296: Testing Olaparib in Patients With Advanced or Metastatic (Cancer That Has Spread) Bladder Cancer and Other Genitourinary Tumors With DNA-Repair Genetic Changes (clinicaltrials.gov)
    P2, N=60, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension • Tumor mutational burden
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • POLE (DNA Polymerase Epsilon) • CCND1 (Cyclin D1) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • BRD4 (Bromodomain Containing 4) • DOT1L (DOT1 Like Histone Lysine Methyltransferase) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • FANCC (FA Complementation Group C)
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    PALB2 mutation • BRIP1 mutation
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    FoundationOne® CDx • FoundationOne® Liquid CDx
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    Lynparza (olaparib)