^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    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
    A phase II clinical trial of epalolitoporvorellimab (QL1706) in combination with fruquintinib for the treatment of immunocompetent pMMR/MSS metastatic colorectal cancer that has failed second- or higher lines of therapy. (ChiCTR2500112464)
    P2, N=18, Not yet recruiting, Harbin Medical University Affiliated Cancer Hospital; Harbin Medical University Affiliated Cancer Hospital
    New P2 trial
    |
    PD-L1 (Programmed death ligand 1) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • CD8 (cluster of differentiation 8) • KMT2A (Lysine Methyltransferase 2A) • POLD1 (DNA Polymerase Delta 1)
    |
    ARID1A mutation
    |
    Fruzaqla (fruquintinib) • Qibeian (iparomlimab/tuvonralimab)
    6d
    Molecular Classification and Clinical Outcomes in Endometrial Cancer: Real-World Evidence from a Tertiary Care Center. (PubMed, Cancers (Basel))
    MMR and p53 IHC serve as practical frontline tools, while POLE sequencing should be prioritized for intermediate- and high-risk endometrioid tumors. Expanded molecular testing in Asian populations is essential to refine risk stratification and optimize individualized management.
    Clinical data • Journal • HEOR • Real-world evidence
    |
    POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)
    |
    TP53 mutation • MSI-H/dMMR • POLE mutation • POLD1 mutation
    |
    Idylla™ POLE-POLD1 Mutation Assay
    6d
    Common gene mutations in 103 authenticated colorectal cancer cell lines. (PubMed, Oncogenesis)
    Genetic interactions based on co-occurring mutations identified cell lines representative of particularly aggressive subtypes of CRC, including concurrent BRAF p.V600 and truncating APC mutations, as well as APC/TP53/RAS triple mutations with double hits of APC. This study provides a resource to guide the selection of cell lines for functional studies of CRC, and detailed mutation data including classifications of pathogenicity, variant allele frequencies and illustrations of the mutation distribution along the length of encoded proteins are included.
    Preclinical • Journal
    |
    BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • APC (APC Regulator Of WNT Signaling Pathway) • RAS (Rat Sarcoma Virus)
    |
    TP53 mutation • BRAF mutation • BRAF V600 • POLE mutation • RAS mutation
    8d
    Tumor mutational burden predicts neoantigen profiles and immunotherapy response in microsatellite stable tumors across different cancer types. (PubMed, Front Immunol)
    We also found that MSS tumors with high TMB have a substantially higher number of neoantigens compared to low-TMB MSS tumors, suggesting they may respond better to immunotherapy, including a high proportion of predicted high-affinity neoantigens. These findings support the clinical relevance of TMB as a biomarker for neoantigen prediction and immunotherapy-relevant features in MSS tumors.
    Journal • Tumor mutational burden • MSi-H Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
    |
    TMB-H • MSI-H/dMMR • TMB-L
    11d
    Clonal Progression of a DNA Polymerase Epsilon-Mutant Endometrial Cancer With Immune Evasion Characteristics and Metastasis. (PubMed, Lab Invest)
    In contrast, metastatic lesions exhibited POLE loss and activation of the BRAF V600E/PIK3CD pathway, leading to progress and immune evasion. These findings highlight a distinct evolutionary trajectory of POLE-mutated EC under immunosuppressive conditions in this case and underscore the need for tailored oncological surveillance and treatment strategies in transplant recipients.
    Journal
    |
    BRAF (B-raf proto-oncogene) • POLE (DNA Polymerase Epsilon) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
    |
    BRAF V600E • BRAF V600 • POLE mutation
    12d
    An interpretable deep learning model for predicting endometrial cancer molecular subtypes from H&E-stained slides. (PubMed, NPJ Precis Oncol)
    Morphological analysis revealed that MSI-H-subtype tumors exhibited increased stromal lymphocytic infiltration; POLEmut tumors showed higher heterogeneity, solid growth patterns, and elevated tumor grade; p53abn tumors were characterized by papillary growth and serous-like features; while NSMP tumors demonstrated high stromal cellularity. This method provides an accurate and interpretable tool for molecular subtype prediction, offering a theoretical basis for future individualized treatment strategies in endometrial cancer.
    Journal • MSi-H Biomarker
    |
    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
    |
    MSI-H/dMMR • POLE mutation
    21d
    The clinical landscape of POLE-mutant colorectal cancer: a retrospective analysis of real-world outcome. (PubMed, BMC Med)
    Pathogenic POLE-mutant CRC constitutes a relatively rare, yet clinically important, subtype. These cancers exhibit distinct clinicopathological and genomic features. Our results indicate that mutations in the POLE gene may serve as a valuable prognostic marker and a potential indicator of benefit to immunotherapy in CRC, offering promising avenues for personalized treatment strategies.
    Retrospective data • Journal • Real-world evidence • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon)
    |
    POLE mutation
    21d
    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, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date • Tumor mutational burden
    |
    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)
    |
    PALB2 mutation • BRIP1 mutation
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    Lynparza (olaparib)
    27d
    FEMUS: Refining Fertility-sparing Treatment in Endometrial Carcinoma Based on Molecular Classification (clinicaltrials.gov)
    P2/3, N=260, Not yet recruiting, Fudan University
    New P2/3 trial • Tumor mutational burden
    |
    PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
    |
    ER positive • MSI-H/dMMR
    |
    Tyvyt (sintilimab) • letrozole • triptorelin • megestrol
    29d
    Phenotypic POLE variant classification identifies patients who may have favorable prognosis and benefit from immunotherapy. (PubMed, J Mol Diagn)
    pPOLE have been incorporated into treatment guidelines for several malignancies and are an important predictor of immunotherapy response. This study provides biological insight to guide classification and clinical management of patients with tumors harboring pPOLE.
    Journal • Tumor mutational burden • MSi-H Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • DRD (DNA Repair Deficiency)
    |
    MSI-H/dMMR • DDR • POLE mutation
    1m
    Molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer (PORTEC-4a): results of a randomised, open-label, phase 3, multicentre, non-inferiority trial. (PubMed, Lancet Oncol)
    Individualised adjuvant treatment by molecular integrated risk profile is safe and effective for patients with high-intermediate risk endometrial cancer; it spared 46% of patients with a favourable profile from adjuvant treatment, and reduces both overtreatment and undertreatment.
    Clinical • P3 data • Journal • Head-to-Head
    |
    POLE (DNA Polymerase Epsilon) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • L1CAM (L1 cell adhesion molecule)
    |
    MSI-H/dMMR • POLE mutation