POLE mutation

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.

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.

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.

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.

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.

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.

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.

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.

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.

Patients with POLE-mutated EC exhibit high SUVmax in primary tumors and also tend to show elevated uptake in non-metastatic lymph nodes.

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.