TMB-H

Elucidating these pathways will be critical for optimizing treatment strategies and improving clinical outcomes in malignancies such as NSCLC. This review highlights the critical role of these pathways in optimizing treatment strategies and improving clinical outcomes in malignancies such as NSCLC.

Multiple-classifier ECs represent a small but clinically relevant subset encompassing biologically heterogeneous entities. Our findings highlight the limitations of current molecular classification hierarchies and underscore the need for harmonized molecular testing and standardized reporting to improve risk stratification and the management of multiple-classifier ECs.

Conversely, PD-L1 and gender showed no consistent predictive value, whereas cutaneous immune-related adverse events and ctDNA reflected favorable and poor outcomes, respectively. These findings highlight the multifactorial nature of immunotherapy response and support the further development of integrated prognostic models to refine patient stratification and optimize treatment outcomes.

Larger multicenter cohorts are needed to validate pathway-oriented patterns and clarify the clinical utility of extreme TMB thresholds across various histologies. Integrating the functional context (e.g., MSI status, gene-level context, and pathway-level features) with TMB magnitude may enable more robust, tumor-aware biomarker models for immunotherapy selection.

Overall, these findings demonstrate that EMS can detect both intrinsic TMB differences and experimentally induced increases in mutational burden, enabling refined categorization of cancer cells. Although further validation is required, this work lays the foundation for developing complementary, rapid, and accessible tools to support cancer cell stratification and guide immunotherapy decision-making.

Notably, the null pattern appeared exclusively in ECs with pathogenic POLE mutations. These results suggest that ATM IHC staining is an effective screening tool for identifying patients who may benefit from confirmatory POLE sequencing among those lacking MMR deficiency or p53 abnormalities.

All findings were classified as ESCAT Tier IIorIII. Our findings support the value of integrating genomic and clinical data to accelerate translational research in rare tumours.

We identified and constructed a 9-RBP based scoring model and a clinical prognostic nomogram for accurately predicting the survival probability and assessing the tumor microenvironment of patients with BRCA. Moreover, our findings firstly demonstrated that RPL9 downregulation correlated with poor clinical outcomes and functionally drives tumor cell proliferation, establishing it as a potential therapeutic target and prognostic biomarker for BRCA.

BRCA2-loss CAPC displays a distinct genomic landscape, marked by robust HRD features, suggesting the potential of higher sensitivity to PARPi. These findings highlight the relevance of HRDsig, and routinely use of CGP in refining patient selection for PARPi and guiding the design of future clinical trials.

Nomograms developed by integrating clinical features and risk scores displayed high predictability. The findings provide new molecular markers and potential therapeutic targets for the prognosis of LUAD and lay a theoretical foundation for the development of therapeutic approaches targeting the NECSO mechanism in patients with LUAD.

We also found that karyotype has limited utility in the setting of NB. Based on this data, we developed an institutional workflow for NB, including MYCN FISH, CMA, and NGS.

Importantly, the imidazotetrazine agent N3-(2-fluoroethyl) imidazotetrazine (KL-50) bypassed MMR dependence and overcame temozolomide resistance. These findings suggest MMR deficiency in GBM as a driver of immune suppression rather than tumor immunogenicity and carry important implications for therapy selection.