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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
    8d
    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
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    TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon)
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    POLE mutation
    8d
    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
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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)
    14d
    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
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    PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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    ER positive • MSI-H/dMMR
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    Tyvyt (sintilimab) • letrozole • triptorelin • megestrol
    16d
    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
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • DRD (DNA Repair Deficiency)
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    MSI-H/dMMR • DDR • POLE mutation
    26d
    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
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    POLE (DNA Polymerase Epsilon) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • L1CAM (L1 cell adhesion molecule)
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    MSI-H/dMMR • POLE mutation
    27d
    The Heterogeneous Interplay Between Metabolism and Mitochondrial Activity in Colorectal Cancer. (PubMed, J Pers Med)
    Using the two R-packages, we functionally confirmed both regulation of metabolism and mitochondrial activities in LOVO cells after stimulation with metformin...Machine learning using Elastic-net allowed us to build a mixed metabolism/mitochondrial activity score, which was found to be increased in the CMS1-MSI subtype and metastatic samples and to be an independent parameter predictive of BRAF-V600E mutation status in colorectal cancer. These findings underscore the pivotal role of mitochondrial metabolism in colorectal cancer subtyping and highlight its value as a predictive biomarker for personalized therapeutic strategies.
    Journal • MSi-H Biomarker
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)
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    TP53 mutation • BRAF V600E • MSI-H/dMMR • BRAF V600 • POLE mutation
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    metformin
    28d
    A Deeper Dive into POLE-Mutated Endometrial Carcinomas: The Contributions and Consequences of Tumor Mutational Burden. (PubMed, Am J Surg Pathol)
    Although our cohort is small, the morphology of POLEmut ECs appears to be influenced by TMB, a phenomenon not yet described in the evolving landscape of these tumors. Taken in combination with differences in underlying genomic signatures, these findings provide an interesting springboard for better understanding POLEmut EC pathobiology.
    Journal • Tumor mutational burden • BRCA Biomarker
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    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler)
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    TMB-H • PIK3CA mutation • PTEN mutation • ARID1A mutation • POLE mutation
    28d
    Elevated 18F-FDG uptake in non-metastatic lymph nodes of POLE-mutated endometrial cancer on PET/CT. (PubMed, Eur J Radiol)
    Patients with POLE-mutated EC exhibit high SUVmax in primary tumors and also tend to show elevated uptake in non-metastatic lymph nodes.
    Journal
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    POLE (DNA Polymerase Epsilon)
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    POLE mutation
    29d
    Molecular Pathology of Ovarian Endometrioid Carcinoma: A Review. (PubMed, Oncol Res)
    We aimed to synthesize contemporary evidence spanning epidemiology, histopathology and immunophenotype, diagnostic pitfalls and differential diagnosis, and to evaluate the clinical utility of The Cancer Genome Atlas (TCGA)-surrogate molecular classification for risk stratification; we also summarize implications for Lynch screening, genetic counseling, and therapeutic opportunities including immune checkpoint inhibitors and targeted approaches, with practical recommendations for diagnostic workflows. Integrating morphology with molecular classification refines diagnosis and prognostication: POLEmut/MMRd subsets generally have excellent outcomes and are candidates for de-escalation or immunotherapy, whereas p53abn/high-grade tumors carry a poorer prognosis and may warrant intensified management and trials of homologous recombination deficiency (HRD)-directed strategies; routine MMR immunohistochemistry (IHC) with reflex germline testing improves Lynch detection, and future priorities include prospective validation and multi-omics to refine NSMP and identify new targets.
    Review • Journal • IO biomarker
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    HRD (Homologous Recombination Deficiency) • POLE (DNA Polymerase Epsilon)
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    MSI-H/dMMR • HRD
    1m
    The molecular cartography of malignant and benign sebaceous tumours. (PubMed, Nat Commun)
    The most frequently mutated gene is NOTCH1. Extensive fusion gene, expression and molecular cluster analyses provide a molecular portrait of this rare and enigmatic tumour type.
    Journal • Tumor mutational burden
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1) • HRNR (Hornerin)
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    TP53 mutation • TMB-H • MSI-H/dMMR • POLE mutation • RB1 deletion • RB1 mutation • POLD1 mutation
    1m
    Association between molecular classification and overall survival in patients with metastatic endometrial carcinoma: ancillary results of the UTOLA phase II GINECO trial. (PubMed, Int J Gynecol Cancer)
    Integration of molecular sub-group as a stratification parameter might be considered for randomized trials in advanced/metastatic endometrial carcinoma after carboplatin-based chemotherapy. Deeper characterization of mismatch repair-proficient tumors might enhance prognostication.
    P2 data • Journal • Tumor mutational burden • PARP Biomarker
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • POLE (DNA Polymerase Epsilon) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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    TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • PTEN mutation • POLE mutation • KRAS wild-type • TMB-L
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    Lynparza (olaparib) • carboplatin
    1m
    Surgical stage in the era of molecular profiling of endometrial cancer. (PubMed, Eur J Cancer)
    Surgical stage remains a strong prognostic factor across molecular subtypes and should be considered alongside molecular classification when tailoring adjuvant treatment in EC.
    Journal
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    TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)
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    TP53 mutation • MSI-H/dMMR • POLE mutation