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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
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Entrez ID:
12d
The exciting journey of progress: Exploring FIGO 2023 staging for endometrial cancer at a leading ESGO institution. (PubMed, Eur J Surg Oncol)
The FIGO 2023 staging system is gaining importance as recent studies highlight the role of molecular classification in prognosis and personalized therapy. Updating our study's follow-up data will clarify its impact in clinical practice.
Journal
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POLE (DNA Polymerase Epsilon)
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POLE mutation
17d
Endometrial cancer (PubMed, Dtsch Med Wochenschr)
In metastatic disease, in mismatch repair proficient cases, the combination of carboplatin and paclitaxel chemotherapy with durvalumab has been recently approved as first line therapy in the European Union, followed by maintenance therapy with the PARP inhibitor olaparib, in combination with durvalumab. For MMRd tumors, several immune checkpoint inhibitors in combination with chemotherapy or as monotherapy have been approved in recent years. Tumors that are overexpressing Her2/neu have an additional treatment option with trastuzumab.
Review • Journal • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
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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 • MSI-H/dMMR • HER-2 overexpression • POLE mutation
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Herceptin (trastuzumab) • Lynparza (olaparib) • carboplatin • Imfinzi (durvalumab) • paclitaxel
19d
OPTEC: Universal Endometrial Cancer DNA Sequencing for Detection of Lynch Syndrome and Personalized Care (clinicaltrials.gov)
P=N/A, N=1001, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Trial completion date: Jun 2023 --> Dec 2025 | Trial primary completion date: Jun 2023 --> Dec 2025
Trial completion date • Trial primary completion date
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MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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POLE mutation
19d
Sample size required for prognostic genes analysis in colorectal cancer. (PubMed, Discov Oncol)
This study shows the relationship between the number of prognostic genes and sample size in CRC and how mutation data affects this relationship. This will contribute to the trial design for prognostic genetic analysis in CRC.
Journal • MSi-H Biomarker
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MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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MSI-H/dMMR • POLE mutation
21d
Pre-operative Targeted Treatments in Molecularly Selected Resectable Colorectal Cancer (UNICORN) (clinicaltrials.gov)
P2, N=112, Recruiting, Gruppo Oncologico del Nord-Ovest | Trial primary completion date: May 2025 --> May 2026
Trial primary completion date
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)
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HER-2 positive • MSI-H/dMMR • KRAS G12C • HER-2 amplification • HER-2 mutation • POLE mutation • KRAS wild-type • RAS wild-type • KRAS G12 • POLD1 mutation • HER-2 positive + HER-2 overexpression • HER-2 positive + RAS wild-type
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Imfinzi (durvalumab) • Vectibix (panitumumab) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Lumakras (sotorasib) • balstilimab (AGEN2034) • botensilimab (AGEN1181)
27d
NCI-2022-09458: FOLFOX and Bevacizumab in Combination With Botensilimab and Balstilimab (3B-FOLFOX) for the Treatment of Microsatellite Stable (MSS) Metastatic Colorectal Cancer (clinicaltrials.gov)
P1/2, N=20, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=86 --> 20
Enrollment closed • Enrollment change
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POLE (DNA Polymerase Epsilon)
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POLE mutation
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Avastin (bevacizumab) • oxaliplatin • leucovorin calcium • balstilimab (AGEN2034) • botensilimab (AGEN1181) • fluorouracil topical
27d
Prediction of molecular subtypes for endometrial cancer based on hierarchical foundation model. (PubMed, Bioinformatics)
The codes and data used for generating results in this study are available at https://github.com/HaoyuCui/hi-UNI for GitHub and https://doi.org/10.5281/zenodo.14627478 for Zenodo. Supplementary data are available at Bioinformatics online.
Journal
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POLE (DNA Polymerase Epsilon)
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TP53 mutation • MSI-H/dMMR • POLE mutation
28d
Unveiling immunogenic characteristics and neoantigens in endometrial cancer with POLE hotspot mutations for improved immunotherapy. (PubMed, Front Immunol)
Importantly, by using an organoid model of EC, we further confirmed the antitumor potential of T cells that were specific to the POLEP286R mutation. Our study uncovers the pronounced immunogenicity of POLE-mutant EC and characterizes neoantigens that are unique to the POLEP286R mutation, thus providing a promising new immunotherapeutic strategy for EC.
Journal • IO biomarker
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POLE (DNA Polymerase Epsilon)
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POLE mutation
30d
Molecular characterization of mixed-histology endometrial carcinoma provides prognostic and therapeutic value over morphologic findings. (PubMed, NPJ Precis Oncol)
Transcriptional analysis demonstrated 93 differentially expressed genes between p53abnl and NSMP tumors, including many associated with the innate immune response and DNA damage repair. While p53abnl and NSMP tumors have similarly poor outcomes, transcriptome analysis revealed biologic differences that could impact targeted therapeutics in this high-risk group.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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TP53 mutation • MSI-H/dMMR • POLE mutation
1m
Journal • Checkpoint inhibition • Tumor mutational burden • Microsatellite instability • IO biomarker
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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TMB-H • POLE mutation
1m
Performance of molecular classification in predicting oncologic outcomes of fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer. (PubMed, Int J Gynecol Cancer)
Molecular classification indicates prognostic value in fertility-sparing treatment for endometrial cancer. NSMP had the highest response rates, whereas MMRd/MSI-H and p53abn were associated with poorer outcomes.
Clinical • Review • Journal • MSi-H Biomarker
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TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
|
TP53 mutation • MSI-H/dMMR • POLE mutation
1m
The prognostic impact of molecular classification in endometrial cancer that undergoes fertility-sparing treatment. (PubMed, Int J Gynecol Cancer)
Although the small number of patients limits our findings, a lower proportion of MMRd responded to progestins than of NSMP.
Retrospective data • Journal
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TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)
|
TP53 mutation • POLE mutation
1m
POLE mutations in endometrial carcinoma: Clinical and genomic landscape from a large prospective single-center cohort. (PubMed, Cancer)
The present findings confirm the absence of significant genomic differences among POLEmut patients regardless of multiple-classifier status or association with high-risk clinical features. Prognostic data will be essential to elucidate the clinical significance of POLE mutations not classified as hotspots that exhibit genomic characteristics similar to those in POLEmut patients.
Journal • Tumor mutational burden
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TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon)
|
POLE mutation
1m
PD-1 and PD-L1 Expression in Endometrial Cancer: A Systematic Review of the Literature. (PubMed, J Clin Med)
Differences in PD-L1 expression between primary and metastatic sites were also noted, complicating its use as a biomarker. The assessment of PD-L1 expression in EC could represent a valuable option for selecting patients who may benefit from immune checkpoint inhibitors (ICI), including those in the MSS cohort, thereby ensuring a more tailored and personalized treatment strategy.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • PD-1 (Programmed cell death 1)
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PD-L1 expression • MSI-H/dMMR • POLE mutation
1m
Analysis of Differences in the Classification of Endometrial Cancer Patients in Poland. (PubMed, Cancers (Basel))
Addressing these variations through standardized diagnostic protocols and equitable access to molecular tools is critical for optimizing patient outcomes. Future research should focus on evaluating the impact of molecular markers on therapy response and prognosis to guide personalized treatment strategies.
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
2ms
Molecular subtype of ovarian clear cell carcinoma: an analysis of 80 Chinese patients using the TCGA molecular classification of endometrial cancer. (PubMed, BMC Cancer)
We did not find prognostic significance of TCGA molecular subtyping in OCCC. POLEmuts are extremely rare, and the incidence of MSI-H and p53abn tumours is also quite low. Further subtyping of the NSMP subgroup is warranted.
Journal • MSi-H Biomarker
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon)
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TP53 mutation • MSI-H/dMMR • PIK3CA mutation • ARID1A mutation • POLE mutation
2ms
Cervical stromal invasion and molecular characterization in stage II-IV endometrial cancers. (PubMed, Gynecol Oncol)
Traditional risk factors such as grade and stage remain critical in determining the prognosis of endometrial cancer with cervical stromal invasion. This study highlights the importance of integrating both molecular and morphological features in determining the prognosis of endometrial cancer, with particular emphasis on endometrioid histotypes.
Journal
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POLE (DNA Polymerase Epsilon)
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TP53 mutation • POLE mutation
2ms
Immune Checkpoint Blockade Delays Cancer Development and Extends Survival in DNA Polymerase Mutator Syndromes. (PubMed, Cancer Res)
These results demonstrated the efficiency by which cells with antigenic mutations are eliminated in vivo. Finally, ICB treatment of mutator mice earlier, before observable tumors had developed delayed cancer onset, improved survival, and selected for tumors without aneuploidy, suggesting the potential of ICB in high-risk individuals for cancer prevention.
Journal • Checkpoint inhibition • Tumor mutational burden • IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)
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TP53 mutation • KRAS mutation • POLE mutation • TP53 deletion • POLD1 mutation • KRAS deletion
2ms
Analysis Of Concordance Between Mismatch Repair Deficiency By Immunohistochemistry And Microsatellite Instability By Next Generation Sequencing In Endometrial And Colorectal Cancer Patients: Results From A Comprehensive Cancer Genome Profiling Programme. (ESGO 2025)
Conclusion NGS-MSI presented different levels of concordance with IHC-MMR among EC and CRC cohorts with EC patients showed a lower concordance rate. Given the predictive role for immunotherapy and the relevance for LS screening, it is important to define a tumor-specific thresholds to reduce false negatives and improve management decisions.
Clinical • Next-generation sequencing • Mismatch repair • Microsatellite instability • IO biomarker • Discordant
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MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6)
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MSI-H/dMMR • POLE mutation
2ms
Molecular classification of endometrial cancer: Impact on adjuvant treatment planning. (PubMed, Cytojournal)
After the integration of molecular classification, a change was observed in the final MDT board decision in 23 cases (35.4%), including six cases of overtreatment and 17 cases of undertreatment, with statistical significance (P = 0.03469). The data suggest that the new molecular classification, that is, testing for POLE mutation, MSI, and p53 mutation and for endometrial carcinoma, is a valuable tool for the recurrence risk prognosis and improved planning of adjuvant treatment for EC.
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
3ms
Actionable mutations in early-stage ovarian cancer according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT): a descriptive analysis on a large prospective cohort. (PubMed, ESMO Open)
These findings highlight the potential for actionable alterations in most early-stage EOC patients and support the exploration of chemotherapy-free regimens for low- to intermediate-risk groups, as well as targeted maintenance therapy for high-risk individuals.
Journal • BRCA Biomarker
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BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • POLE (DNA Polymerase Epsilon)
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BRAF V600E • BRCA2 mutation • BRCA1 mutation • PIK3CA mutation • BRAF V600 • POLE mutation
3ms
Endometrial adenocarcinoma with mutations in POLE, TP53 genes and microsatellite instability (PubMed, Arkh Patol)
At the same time POLE-mutated endometrial carcinomas recur rarely and exhibit the excellent prognosis. Here we report the rare case of 65 y.o. female patient with endometrioid carcinoma sharing immunohistochemical and molecular features of TP53-aberrant, MMR deficient and POLE-mutated subtypes.
Journal • Microsatellite instability
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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
3ms
Next-generation sequencing in the molecular classification of endometrial carcinomas: Experience with 270 cases suggesting a potentially more aggressive clinical behavior of multiple classifier endometrial carcinomas. (PubMed, Virchows Arch)
Our findings suggest that combining immunohistochemistry with NGS offers a more reliable classification of ECs, including 'multiple classifier' cases, which, based on our observations, tend to exhibit aggressive behavior. Additionally, our data highlight the complex genetic background of NSMP ECs, which can facilitate further stratification of tumors within this group and potentially help select patients for dedicated clinical trials.
Journal • Next-generation sequencing
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon)
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TP53 mutation • PIK3CA mutation • PTEN mutation • POLE mutation
3ms
PD-L1 Expression and Immune Infiltration Across Molecular Subtypes of Endometrial Cancer: An Integrative-Analysis of Molecular Classification and Immune Subtypes. (PubMed, Hum Pathol)
Higher CD8+ T cell density was a prognostic marker for disease-free survival in EC, including within NSMP (p<0.05). In summary, the four WHO molecular subtypes of EC exhibit distinct TIME subtypes, complementing molecular classification and providing insights for optimizing EC immunotherapy strategies.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD20 (Membrane Spanning 4-Domains A1) • POLE (DNA Polymerase Epsilon) • CD8 (cluster of differentiation 8) • CD68 (CD68 Molecule)
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PD-L1 expression • TP53 mutation • MSI-H/dMMR • POLE mutation • CD8-H
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VENTANA PD-L1 (SP263) Assay
3ms
Clinicopathological and molecular genetic features of POLE-mutated endometrioid carcinoma (PubMed, Zhonghua Bing Li Xue Za Zhi)
Correct interpretation of molecular results, accurate identification and classification are important for predicting prognosis and avoiding overtreatment. However, a small number of cases may have recurrence and metastasis, and therefore it is necessary to make a reasonable treatment plan based on the comprehensive judgment of other high risk factors.
Retrospective data • 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
3ms
POLE-mutated uterine carcinosarcomas: a clinicopathologic and molecular study of 11 cases. (PubMed, Mod Pathol)
Our study supports full molecular classification of UCS. We also raise awareness for potentially assessing POLE mutation allele fraction and clonality in the consideration of classifying a tumor as POLEmut.
Journal
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • FBXW7 (F-Box And WD Repeat Domain Containing 7)
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TP53 mutation • PIK3CA mutation • PTEN mutation • ARID1A mutation • POLE mutation • TP53 expression
3ms
The advent of immune checkpoint inhibition for the treatment of patients with primary advanced or recurrent dMMR/MSI high endometrial cancer in 2025. (PubMed, Curr Opin Obstet Gynecol)
Immunotherapy therapy has revolutionized the treatment of endometrial cancer in both upfront and recurrent settings, with molecular subtyping identifying patients most likely to benefit, especially those with dMMR/MSI-H tumors.
Journal • Checkpoint inhibition • MSi-H Biomarker • IO biomarker • Metastases
|
MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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MSI-H/dMMR • POLE mutation
4ms
Functions, interactions and prognostic role of POLE: a bioinformatics analysis. (PubMed, J Gynecol Oncol)
Mutations in POLE might affect DNA polymerase epsilon function. These mutations also affect interactions with other proteins like proteins involved in different DNA repairing mechanisms. POLE mutations may lead to platinum resistance, but they can also trigger an immune response that improves prognosis.
Journal
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POLE (DNA Polymerase Epsilon) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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POLE mutation • POLE V411L
4ms
Prognostic and therapeutic implication of molecular classification including L1CAM expression in high-risk endometrial cancer. (PubMed, Gynecol Oncol)
L1CAM is an additional adverse factor in the p53 abnormal and NSMP groups. These groups need special attention in studies intensifying adjuvant treatment.
Journal
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POLE (DNA Polymerase Epsilon) • L1CAM (L1 cell adhesion molecule)
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TP53 mutation • POLE mutation
4ms
Molecular classification and adjuvant treatment in endometrioid endometrial cancer with microcystic elongated and fragmented (MELF) invasion pattern. (PubMed, BMC Womens Health)
The presence of the MELF pattern in EEC should be incorporated into decision-making regarding adjuvant therapy. The use of adjuvant treatment should be tailored based on histology and molecular type.
Retrospective data • Journal
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TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)
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TP53 mutation • MSI-H/dMMR • POLE mutation
4ms
PIK3CA mutations in endometrial cancer: a pre-planned biomarker analysis from the phase II MITO END-3 study of carboplatin and paclitaxel with or without avelumab in advanced or recurrent endometrial cancer (AIOM 2024)
The frequent alterations of the PI3K pathway in gynecological cancers could emerge as new treatment target. Our data confirm the high frequency of PIK3CA mutations establishing EC as an ideal candidate for testing of PI3K inhibitors regardless of the TCGA classification. Moreover, these data confirm that other targetable mutations are present also in MSS EC group thus suggesting that new target agents should be explored.
P2 data • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon)
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TP53 mutation • MSI-H/dMMR • PIK3CA mutation • TP53 wild-type • PIK3CA H1047R • PTEN mutation • ARID1A mutation • POLE mutation • PIK3CA E545K • PIK3CA E545 • PIK3CA E542 • PIK3CA H1047L • PIK3CA mutation + PTEN mutation • PIK3CA C420R • PIK3CA E545A • PIK3CA E545G • PIK3CA Q546 • PIK3CA Q546R
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FoundationOne® CDx
|
carboplatin • paclitaxel • Bavencio (avelumab)
4ms
Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)
4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.
Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
|
BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion
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FoundationOne® CDx
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)
4ms
Advantages of next-generation sequencing (NGS) in the molecular classifi cation of endometrial carcinomas - our experience with 270 cases. (PubMed, Ceska Gynekol)
In comparison with recommended diagnostic algorithms, NGS provides a more reliable classification of EC into particular molecular subgroups. Furthermore, NGS reveals the complex molecular genetic background in individual ECs, which is especially significant within ECs with no specific molecular profile. These data can serve as a springboard for the research of therapeutic programs committed to targeted therapy in this type of tumor.
Journal • Next-generation sequencing • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • BCOR (BCL6 Corepressor) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • POLD1 (DNA Polymerase Delta 1)
|
TP53 mutation • PIK3CA mutation • PTEN mutation • POLE mutation
4ms
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)
5ms
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
5ms
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
5ms
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)
6ms
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
6ms
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
6ms
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
6ms
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
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Keytruda (pembrolizumab) • Tecentriq (atezolizumab)
6ms
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
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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TMB-H • MSI-H/dMMR • POLE mutation
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