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    BIOMARKER:

    POLE mutation

    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
    Entrez ID:
    5426
    Related biomarkers:
    Mutation
    Others
    3d
    Radiation and TSR-042 (Dostarlimab) in People With Endometrial Cancer After They Receive Surgery (clinicaltrials.gov)
    P2, N=62, Recruiting, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Recruiting | N=31 --> 62 | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026
    Enrollment open • Enrollment change • Trial completion date • Trial primary completion date • Checkpoint inhibition • Mismatch repair • Surgery • Checkpoint block • Metastases
    |
    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSI-H/dMMR • POLE mutation
    |
    Jemperli (dostarlimab-gxly)
    1m
    Durvalumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer (clinicaltrials.gov)
    P2, N=33, Completed, Asan Medical Center | Active, not recruiting --> Completed
    Trial completion • Mismatch repair • Tumor mutational burden • Metastases
    |
    POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    MSI-H/dMMR • POLE mutation
    |
    Imfinzi (durvalumab) • oxaliplatin • irinotecan
    1m
    Effect of hemoglobin, albumin, lymphocyte, and platelet score on prognosis in intermediate-risk endometrial cancer according to molecular-based classification. (PubMed, J Obstet Gynaecol Res)
    MMR deficiency and NSMP have been considered intermediate-risk groups for endometrial cancer and are a heterogeneous group. Although the use of the HALP score to reduce this heterogeneity is successful in predicting OS, it is not sufficient for PFS.
    Journal
    |
    TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)
    |
    TP53 mutation • POLE mutation
    2ms
    A Phase 1 Trial of Trebananib, an Angiopoietin 1 and 2 Neutralizing Peptibody, Combined with Pembrolizumab in Patients with Advanced Ovarian and Colorectal Cancer. (PubMed, Cancer Immunol Res)
    After development of acquired resistance, biopsy of one patient's KRAS wild-type, ERBB2 amplified tumor showed a substantial decline in tumor-associated T cells and an increase in immunosuppressive intratumoral macrophages. Future studies are needed to carefully assess whether clinicogenomic features, such as lack of liver metastases, ERBB2 amplification, and left-sided tumors, can predict increased sensitivity to PD1 immunotherapy combinations.
    P1 data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • POLE (DNA Polymerase Epsilon)
    |
    HER-2 amplification • POLE mutation • KRAS wild-type • RAS wild-type
    |
    Keytruda (pembrolizumab) • trebananib (AMG 386)
    2ms
    Predictors of Node Positivity in Endometrial Cancer (clinicaltrials.gov)
    P=N/A, N=200, Recruiting, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano | Not yet recruiting --> Recruiting | N=100 --> 200 | Trial completion date: Dec 2023 --> Jan 2025 | Trial primary completion date: Dec 2023 --> Dec 2024
    Enrollment open • Enrollment change • Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
    |
    TP53 mutation • MSI-H/dMMR • POLE mutation
    2ms
    Deciphering the immune landscape of gastro-entero-pancreatic high-grade neuroendocrine neoplasms could help in tailoring medical treatment? (ECP 2024)
    Immunotherapy has shown poor efficacy in the unselected population of HG-GEP-NENs because the immune microenvironment landscape was scant in HG-GEP-NENs at transcriptomic analysis and PD-L1 expression was absent. Thus, there is a great need to identify subsets of HG-GEP-NENs responsive to immunotherapy approaches. The present results addressed GEP-NECs with high proliferation index as sensible candidates to immunotherapy due to the enrichment in TMB-high and MSI coupled with higher CD4+ and CD8+ T cell expression.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • CD8 (cluster of differentiation 8) • MSH2 (MutS Homolog 2) • CD4 (CD4 Molecule)
    |
    PD-L1 expression • TMB-H • PD-L1 negative • POLE mutation
    |
    TruSight Oncology 500 Assay
    2ms
    Clinical implications of next generation sequencing for the classification of endometrial carcinoma (ECP 2024)
    Molecular characterization of endometrial carcinoma into subgroups has important implications for prognosis and treatment. Next-generation sequencing is a powerful tool that provides reliable results consistent with surrogate immunohistochemical markers. By performing a molecular profile of patients, NGS can identify important genetic mutations such as p53, POLE and MSI, as well as variants like CTNNB1 that have prognostic value.
    Clinical • Next-generation sequencing
    |
    TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    TP53 mutation • POLE mutation • TP53 expression
    |
    OncoKitDx
    2ms
    High tumour mutation burden assessed by comprehensive molecular genetic profiling as a targeted therapeutic option for solid tumours (ECP 2024)
    Eight patients received immune checkpoint inhibitor therapy (7 pembrolizumab and 1 atezolizumab). TMB status determined by CGP was found to be an effective method for predicting the response to immune checkpoint inhibitors; both PFS and OS improved markedly for patients who received therapy. In our experience, TMB status, along with microsatellite instability and POLE mutation status, can be used as a predictive biomarker for therapeutic response in a wide range of histologies.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
    |
    TMB-H • POLE mutation
    |
    Oncomine™ Comprehensive Assay Plus
    |
    Keytruda (pembrolizumab) • Tecentriq (atezolizumab)
    2ms
    Concurrent POLE hotspot mutations and mismatch repair deficiency/microsatellite instability in endometrial cancer: A challenge in molecular classification. (PubMed, Gynecol Oncol)
    POLEmut/MMRd ECs may be genetically distinct. Further studies are needed to assess the impact on outcomes and treatment response within this population.
    Journal • Mismatch repair • Tumor mutational burden • Microsatellite instability • MSi-H Biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
    |
    TMB-H • MSI-H/dMMR • POLE mutation
    2ms
    The game-changing impact of POLE mutations in oncology-a review from a gynecologic oncology perspective. (PubMed, Front Oncol)
    Therapeutic modalities for these hypermutated tumors are also an important consideration, including the need for or de-escalation of adjuvant treatments and the response to immune therapy. This review addresses the critical role of POLE mutations in gynecologic oncology and oncology in general, focusing on definitions, variants, underlying pathogenic mechanisms, upcoming developments in the field, and the clinic behavior associated with such mutations.
    Review • Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon)
    |
    TMB-H • POLE mutation • POLE EDM
    2ms
    Endometrial carcinomas with ambiguous histology often harbor TP53 mutations. (PubMed, Virchows Arch)
    In conclusion, based on this series, the molecular landscape of endometrial carcinomas with ambiguous histology is dominated by TP53 mutations and the absence of POLE mutations, with heterogeneous molecular profile with respect to other genes. A high proportion of these tumors is clinically aggressive.
    Journal • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • MUC16 (Mucin 16, Cell Surface Associated) • FAT1 (FAT atypical cadherin 1) • JAK1 (Janus Kinase 1) • FAT4 (FAT Atypical Cadherin 4) • CSMD3 (CUB And Sushi Multiple Domains 3) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
    |
    TP53 mutation • PIK3CA mutation • POLE mutation
    6ms
    A comprehensive analysis of POLE/POLD1 genomic alterations in colorectal cancer. (PubMed, Oncologist)
    Patients with POLE/POLD1 mutations exhibited significant differences across immunological markers (ie, TMB, MMR, and MSI-H) and molecular co-alterations. Those with short variant mutations represented 18% of the POLE/POLD1 cohort and 0.4% of the total cohort examined. This group of patients had a median TMB of 159 mut/Mb (range 34-488), representing the ultra-hypermutated phenotype. This group of patients is important to identify given the potential for exceptional response to immune checkpoint inhibitors.
    Journal • Tumor mutational burden • MSi-H Biomarker • BRCA Biomarker • IO biomarker
    |
    ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)
    |
    TMB-H • MSI-H/dMMR • ATM mutation • POLE mutation • ALK mutation • RET mutation • POLD1 mutation • POLE mutation + POLD1 mutation
    |
    Tempus xT Assay
    6ms
    Value of Molecular Typing Combined with Integrated Positron Emission Tomography/Magnetic Resonance Imaging in Risk Stratification of Endometrial Cancer. (PubMed, Int J Womens Health)
    Molecular typing combined with the integrated PET/MRI semi-quantitative SUV max index can predict the low/medium risk group of endometrial cancer and the medium-high/high risk group, and the cut-off value of SUV max for predicting the risk of early endometrial cancer was 14.72 (sensitivity 66.7%, specificity 68.7%). Molecular typing combined with integrated PET/MRI semi-quantitative indicators is useful to achieve risk stratification in patients diagnosed with endometrial cancer and guide individualized treatment.
    Journal • MRI
    |
    TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)
    |
    POLE mutation
    6ms
    Enrichment for the POLE mutated against p53 wild subtype using clinicopathologic factors and cyclin B1 immunohistochemistry in endometrial cancer. (PubMed, J Gynecol Oncol)
    No abstract available
    Journal
    |
    TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon) • CCNB1 (Cyclin B1)
    |
    TP53 mutation • POLE mutation
    6ms
    MITO END-3: Efficacy of Avelumab immunotherapy according to molecular profiling in first-line endometrial cancer therapy. (PubMed, Ann Oncol)
    The MITO END-3 trial results suggest that TP53 mutation is associated with a poor effect of avelumab, while mutations of PTEN and ARID1A are related to a positive effect of the drug in patients with advanced endometrial cancer.
    Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon)
    |
    TP53 mutation • BRCA2 mutation • BRCA1 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • TP53 wild-type • PTEN mutation • ARID1A mutation • POLE mutation
    |
    carboplatin • paclitaxel • Bavencio (avelumab)
    7ms
    Prognostic value of molecular classification in stage IV endometrial cancer. (PubMed, Int J Gynecol Cancer)
    The distribution of the molecular subclasses in stage IV endometrial cancer patients differed substantially from the distribution in stage I-III endometrial cancer patients, with the unfavorable subclasses being more frequently present. Although the molecular classification was not prognostic in stage IV endometrial cancer, it could guide adjuvant treatment decisions.
    Journal • Metastases
    |
    ER (Estrogen receptor) • POLE (DNA Polymerase Epsilon)
    |
    ER positive • MSI-H/dMMR • POLE mutation • ER negative
    7ms
    Predicting the Risk of nOdal disease with histological and Molecular features in Endometrial cancer: the prospective PROME trial. (PubMed, Int J Gynecol Cancer)
    Our data suggest that molecular classification does not seem useful to tailor the need of nodal dissection in apparent early-stage endometrial cancer. p53 abnormality predicts the risk of having advanced disease at presentation. Further external validation is needed.
    Journal • MSi-H Biomarker
    |
    TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
    |
    TP53 mutation • MSI-H/dMMR • POLE mutation
    7ms
    Pembrolizumab in Ultramutated and Hypermutated Endometrial Cancer (clinicaltrials.gov)
    P2, N=25, Active, not recruiting, Yale University | Trial completion date: Jun 2024 --> Oct 2025 | Trial primary completion date: Jun 2024 --> Oct 2025
    Trial completion date • Trial primary completion date • IO biomarker
    |
    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)
    |
    POLE mutation • POLD1 mutation • POLE mutation + POLD1 mutation
    |
    Keytruda (pembrolizumab)
    7ms
    Molecular profile in endometrial carcinoma: can we predict the lymph node status? A systematic review and meta-analysis. (PubMed, Clin Transl Oncol)
    The presence of LNM seems to be influenced by molecular classification. P53-abnormal group presents the highest rate of nodal involvement, and POLE-mutated the lowest.
    Retrospective data • Review • Journal
    |
    POLE (DNA Polymerase Epsilon)
    |
    POLE mutation
    7ms
    High prevalence of "non-pathogenic" POLE mutation with poor prognosis in a cohort of endometrial cancer from South India. (PubMed, Int J Gynaecol Obstet)
    This study identified a unique set of POLE mutations in Indian EC patients associated with poor prognosis, which were particularly pronounced in advanced stages. Advanced stage of presentation, type of POLE mutations, and possibly ethnicity are predictors of adverse outcomes in POLE-mutated EC. The present study highlights ethnicity as a determinant of phenotypic expression of genetic change.
    Journal
    |
    POLE (DNA Polymerase Epsilon)
    |
    POLE mutation
    8ms
    Morules and β-catenin predict POLE mutation status in endometrial cancer: A pathway to more cost-effective diagnostic procedures. (PubMed, Am J Clin Pathol)
    Our findings suggest that the presence of either morules or nuclear β-catenin expression in EEC could practically rule out the presence of POLE mutations. These morphologic and immunohistochemical features can be used as preliminary screening tools for POLE mutations, offering significant savings in time and resources and potentially enhancing clinical decision-making and patient management strategies. However, further validation in larger, multi-institutional studies is required to fully understand the implications of these findings on clinical practice.
    Journal • HEOR • Cost-effectiveness • Cost effectiveness
    |
    POLE (DNA Polymerase Epsilon) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    POLE mutation
    8ms
    Pembrolizumab in Ultramutated and Hypermutated Endometrial Cancer (clinicaltrials.gov)
    P2, N=25, Active, not recruiting, Yale University | Trial completion date: Dec 2028 --> Jun 2024 | Trial primary completion date: Dec 2023 --> Jun 2024
    Trial completion date • Trial primary completion date • IO biomarker
    |
    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)
    |
    POLE mutation • POLD1 mutation • POLE mutation + POLD1 mutation
    |
    Keytruda (pembrolizumab)
    8ms
    Assessing the New 2020 ESGO/ESTRO/ESP Endometrial Cancer Risk Molecular Categorization System for Predicting Survival and Recurrence. (PubMed, Cancers (Basel))
    The 2020 ESGO molecular classification system demonstrated practical utility and significantly influenced survival outcomes. Immunohistochemistry for TP53 and MMR, along with POLE sequencing, facilitated substantial patient reclassification, underscoring the clinical relevance of molecular risk categories in EC management.
    Journal
    |
    TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)
    |
    TP53 mutation • MSI-H/dMMR • POLE mutation
    8ms
    The Clinical and Pathological Characteristics of POLE-Mutated Endometrial Cancer: A Comprehensive Review. (PubMed, Cancer Manag Res)
    This subtype exhibits a high tumor mutation burden, abundant lymphocyte infiltration, and a favorable prognosis, making it a promising candidate for immune checkpoint inhibitor therapy. This paper presents a comprehensive review of the clinical and pathological characteristics, outcomes, treatment advancements, pathogenic POLE gene detection, and alternative testing methods for POLE-mutated endometrial cancer.
    Review • Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon)
    |
    TMB-H • POLE mutation
    9ms
    AcSé: Secured Access to Nivolumab for Adult Patients With Selected Rare Cancer Types (clinicaltrials.gov)
    P2, N=269, Completed, UNICANCER | Active, not recruiting --> Completed
    Trial completion
    |
    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
    |
    POLE mutation
    |
    Opdivo (nivolumab)
    9ms
    Potential of molecular classification to guide fertility-sparing management among young patients with endometrial cancer. (PubMed, Gynecol Oncol)
    Lastly, the no specific molecular profile (or p53 wild-type) tumors, while having a relatively good prognosis, are heterogeneous and require more precise biomarkers to effectively guide therapy for those with poorer prognoses. Addressing these research gaps will lead to more precise guidelines to ensure optimal selection for fertility-sparing treatment.
    Journal
    |
    TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)
    |
    TP53 mutation • MSI-H/dMMR • TP53 wild-type • POLE mutation • TP53 expression • POLE EDM
    9ms
    Tumor mutational burden assessment and standardized bioinformatics approach using custom NGS panels in clinical routine. (PubMed, BMC Biol)
    We herein propose a TMB calculation method and a bioinformatics tool that is customizable to different NGS panels and sample types. We were not able to retrieve TMB values from FO algorithm using our own algorithm and NGS panel.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Next-generation sequencing
    |
    TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon)
    |
    TMB-H • POLE mutation
    |
    FoundationOne® CDx
    |
    Keytruda (pembrolizumab)
    9ms
    Multiple duodenal epithelial tumors in a patient with polymerase proofreading-associated polyposis in POLE variant. (PubMed, Clin J Gastroenterol)
    In addition, duodenal tumors frequently coexist in patients with PPAP-carrying POLE variants, while the endoscopic treatment for duodenal tumors becomes safe and useful with several new approaches. Therefore, surveillance EGD is necessary in such patients for the early detection and treatment of duodenal tumors.
    Journal
    |
    POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)
    |
    POLE mutation
    9ms
    Nivolumab Ipilimumab in Patients With hyperMutated Cancers Detected in Blood (NIMBLe) (clinicaltrials.gov)
    P2, N=4, Terminated, Canadian Cancer Trials Group | Active, not recruiting --> Terminated; cfDNA screening data found that the prevalence of POLE/POLD1 mutations was lower than expected. It was determined that there are no feasible options to amend this study in a fashion that would not be duplicative of other currently accruing trials.
    Trial termination
    |
    POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)
    |
    POLE mutation • POLD1 mutation • POLE mutation + POLD1 mutation
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab)
    9ms
    Molecular profile is a strong predictor of the pattern of recurrence in patients with endometrial cancer. (PubMed, Int J Gynecol Cancer)
    Endometrial cancer featured different patterns of recurrence depending on the molecular profile. p53-abnormal molecular profiling was the only independent risk factor for peritoneal relapse, while non-specific molecular profile showed a strong association with distant failures.
    Journal
    |
    POLE (DNA Polymerase Epsilon)
    |
    TP53 mutation • MSI-H/dMMR • POLE mutation
    9ms
    Correlation of PTEN Alterations with Immunohistochemistry in POLE-Mutated and Mismatch Repair-Deficient Endometrial Carcinoma (USCAP 2024)
    In summary, PTEN IHC expression was retained in the majority of PTEN- and POLE-mutated ECs with frequent missense mutations in codon 130. Some codon 130 mutations (e.g., R130Q) are known to be associated with protein stability. Nearly half of PTEN-mutated MMR-d ECs were associated with PTEN expression (retained, reduced or subclonal loss).
    Mismatch repair
    |
    MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2)
    |
    MSI-H/dMMR • PTEN mutation • POLE mutation • PTEN expression • PMS2 mutation
    |
    Oncomine™ Comprehensive Assay v3M
    9ms
    Dominant Negative PTEN Alterations in Endometrial Carcinomas Are Associated with Positive (Retained or Reduced) Immunohistochemical PTEN Expression (USCAP 2024)
    In summary, our results indicate that PTEN IHC staining is present in majority of ECs with four common dominant-negative PTEN mutations (retained or less commonly reduced). While recent literature suggests complementary use of PTEN IHC and sequencing to assess PTEN status in EC, these results further highlight that IHC may not be helpful in assessment of PTEN abnormality in cases with dominant-negative PTEN mutations.
    PTEN (Phosphatase and tensin homolog) • POLE (DNA Polymerase Epsilon) • ARG1 (Arginase 1)
    |
    TP53 mutation • PTEN mutation • POLE mutation • PTEN expression • PTEN negative
    |
    Oncomine™ Comprehensive Assay v3M
    9ms
    Endometrial Cancers with Low Level Microsatellite Instability: Classification Pitfalls and Practical Recommendations for Assigning Mismatch Repair Status by Next Generation Sequencing with MSIsensor and Ancillary Tests (USCAP 2024)
    MSIsensor scores as low as 3.5% may represent true MMRd in EC tested by NGS. Further testing for MMRd is advised for MSIsensor scores between 3% and 30%, particularly if there is low tumor content or associated high TMB. In this setting, MMR IHC may have superior sensitivity for detection of MMRd compared to DNA-based assays.
    Microsatellite instability • Tumor mutational burden • IO biomarker • Next-generation sequencing • Mismatch repair
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    |
    TMB-H • POLE mutation • MSH6 mutation • MSH2 mutation • PMS2 mutation
    |
    Idylla™ MSI Test
    9ms
    Homologous Recombination Deficiency (HRD) In Primary Advanced Stage And Recurrent P53 Abnormal Endometrial Carcinoma (ESGO 2024)
    Further investigation of HRD and EC-specific GIS cut-off value are highly warranted and may help to improve outcome in this specific EC subgroup. Patients with p53abn tumors may benefit from PARP inhibition and HRD testing may provide key information for patient selection.
    Tumor mutational burden • PARP Biomarker • BRCA Biomarker • Metastases
    |
    TMB (Tumor Mutational Burden) • HRD (Homologous Recombination Deficiency) • POLE (DNA Polymerase Epsilon) • BRCA (Breast cancer early onset)
    |
    TP53 mutation • HRD • POLE mutation • TMB-L • BRCA mutation
    |
    Myriad myChoice® CDx
    9ms
    Impact of molecular profile on prognosis and relapse pattern in low and intermediate risk endometrial cancer. (PubMed, Eur J Cancer)
    The differences in outcome by molecular groups are driven by differences in relapse frequency and -patterns and demand a higher precision in diagnostics, also in patients with low/intermediate risk EC. Tailored adjuvant treatment strategies need to consider systemic treatment for patients with p53 abnormal tumors and de-escalated treatment for patients with POLE mutated tumors.
    Journal
    |
    POLE (DNA Polymerase Epsilon) • L1CAM (L1 cell adhesion molecule)
    |
    TP53 mutation • MSI-H/dMMR • POLE mutation
    9ms
    New therapeutic targets for endometrial cancer: a glimpse into the preclinical sphere. (PubMed, Expert Opin Ther Targets)
    Moreover, the expression of specific molecular signatures offers the possibility to employ novel target therapies, such as immune-checkpoint inhibitors that have demonstrated a significant benefit on prognosis. New treatment guidelines are still being established, and ongoing studies are exploring the potential prognostic role of further sub-stratifications of the four molecular classes and treatment options.
    Preclinical • Review • Journal
    |
    TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)
    |
    TP53 mutation • POLE mutation
    10ms
    Exploring Co-occurring POLE Exonuclease and Non-exonuclease Domain Mutations and Their Impact on Tumor Mutagenicity. (PubMed, Cancer Res Commun)
    This study suggests a novel modifier role for POLE variants in POLE ExoD-driven tumors, associated with ultra-high TMB. These data, in addition to future functional studies, may inform tumor classification, therapeutic response, and patient outcomes.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon)
    |
    TMB-H • POLE mutation • TMB-L
    10ms
    The new 2023 FIGO staging system for endometrial cancer: what is different from the previous 2009 FIGO staging system? (PubMed, J Gynecol Oncol)
    The 2023 staging system for EC subdivided stages I and II compared to the 2009 system. The 2023 system with molecular classification is a good predictor of survival.
    Journal
    |
    POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2)
    |
    TP53 mutation • POLE mutation • PMS2 mutation
    10ms
    Tumor characteristics of dissociated response to immune checkpoint inhibition in advanced melanoma. (PubMed, Cancer Immunol Immunother)
    Intrapatient comparison of progressive versus regressive lesions indicates no defect in tumor T cell infiltration, and in general no tumor immune exclusion were observed.
    Journal • Checkpoint inhibition • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • POLE (DNA Polymerase Epsilon) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • B2M (Beta-2-microglobulin)
    |
    PD-L1 expression • PTEN mutation • POLE mutation • CD8-H
    10ms
    Prognosis of polymerase epsilon (POLE) mutation in high-grade endometrioid endometrial cancer: Systematic review and meta-analysis. (PubMed, Gynecol Oncol)
    POLE mutations in high-grade endometrioid EC are associated with a more favorable prognosis with increased OS and PFS.
    Retrospective data • Review • Journal
    |
    POLE (DNA Polymerase Epsilon)
    |
    POLE mutation
    10ms
    The P286R mutation of DNA polymerase ε activates cancer-cell-intrinsic immunity and suppresses endometrial tumorigenesis via the cGAS-STING pathway. (PubMed, Cell Death Dis)
    Furthermore, the POLE P286R mutation inhibits tumor growth and facilitates the infiltration of cytotoxic T cells in human endometrial cancers. These findings uncover a novel mechanism of POLE mutations in antagonizing tumorigenesis and provide a promising direction for effective cancer therapy.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    POLE (DNA Polymerase Epsilon)
    |
    POLE mutation
    10ms
    Somatic POLE Mutation and Ultra-Hypermutated Genotype in a De Novo High-Grade, Isocitrate Dehydrogenase Wild-Type Glioma: Treatment Implications. (PubMed, JCO Precis Oncol)
    Pembrolizumab leads to a durable response in ultra-hypermutated, high-grade, glioma.
    Journal • PD(L)-1 Biomarker
    |
    POLE (DNA Polymerase Epsilon)
    |
    POLE mutation • IDH wild-type
    |
    Keytruda (pembrolizumab)