POLE EDM

Our study demonstrates that the concise NGS panel is an effective 'one-stop' strategy for precisely classifying EC with high clinical availability.

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.

Recently, TCGA molecular subgroups have been integrated into the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging classification which incorporates other non-anatomic parameters like histotype, tumor grade, and lymphovascular space invasion. The result is a complicated and non-intuitive classification that makes its clinical application difficult and does not facilitate correspondence with the 2009 FIGO staging.

P=N/A, N=1000, Recruiting, University Hospital, Gasthuisberg

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.

These findings emphasize the need for integrating tumor sequencing into LS diagnostics, along with clear interpretation guidelines, to improve clinical management. While not impacting prognosis, confirmation of DS-MMRd EC may release patients and relatives from burdensome LS-surveillance.

P1, N=10, Completed, University Medical Center Groningen | Recruiting --> Completed | N=20 --> 10 | Trial completion date: Nov 2022 --> Nov 2023 | Trial primary completion date: May 2022 --> Apr 2023

Our findings highlighted the importance of accurately interpreting heterogeneous MMR protein staining patterns for developing a more efficient personalized genetic investigation strategy.

TP53mut prediction model (TPMM) had good diagnostic accuracy, and survival analysis showed the model can identify patients with different prognostic risk.

Conclusions Our study demonstrates that the concise NGS panel is an effective "one-stop" strategy to precisely classify EC with high clinical availability. Further follow-up data are needed to testify to the effect of the classification on the prognosis of different adjuvant therapies or rare pathological subtypes.

Identification of 'POLE-like' groups may facilitate therapeutic de-escalation in some TP53-mutated cases - a novel option. Instead of 5% (POLE-EDM), potential beneficiary would then comprise 10% (POLE-like) of TCGA-UCEC.

Patients with EOCRC were less likely to have a MMR deficient signature, but more likely to have mutational signatures consistent with damage by ROS, POLE exonuclease domain mutations. Expectedly, more AOCRC cases harbored clock-like signatures related to age. While EOCRC and AOCRC often do not differ significantly on the single gene variant level, this genomic clustering data suggests that EOCRC may be caused by uniquely different mutagenic processes compared to AOCRC.