TMB (Tumor Mutational Burden)

IL-17-responsive, tumor cell-intrinsic inflammatory programming remodels the tumor immune microenvironment toward an immunotherapy-permissive state. These findings establish IL-17-responsive tumor cell inflammatory programming as a mechanistic axis shaping immune checkpoint sensitivity and provide a rationale for biomarker-guided immunotherapy strategies.

We establish a robust, mutation-independent methylation-based liquid biopsy strategy for neuroblastoma that enables accurate, quantitative disease monitoring across all high-risk patients including those lacking trackable genomic alterations. This approach supports clinical translation of methylation-based cfDNA deconvolution as a broadly applicable platform for pediatric precision oncology.

Prospective studies and registry-based analyses are needed to refine risk assessment, optimize management, and maximize the clinical utility of POLE profiling. This review provides a comprehensive and integrative overview of POLE alterations across human cancers, integrating molecular, clinicopathological, and immunological insights with therapeutic implications.

After three cycles of neoadjuvant carboplatin, pemetrexed, and pembrolizumab, computed tomography (CT) scan revealed a significant response. Incorporating a POLE evaluation could improve the integrated decision-making process for patients with NSCLC in the perioperative setting. Prospective studies are warranted to validate this observation.

Given the challenges in diagnosis and the potential for rapid recurrence or metastasis, early detection is crucial. Comprehensive genomic profiling is highly desirable, as genomic analysis may direct the development of targeted therapeutic agents to treat relapse.

CLTC may serve as a prognostic biomarker in OSCC and may contribute to tumor progression by promoting malignant cellular phenotypes and immunosuppressive remodeling of the tumor microenvironment. Future mechanistic studies are required to determine whether CLTC directly regulates chemotherapy response through clathrin-mediated trafficking, receptor recycling, adhesion signaling, or tumor-immune interactions.

In this 106-patient cohort study, we delineated the somatic mutational landscape of thalamic glioma and showed that 9p21 loss is mutually exclusive with H3F3A mutations, providing a highly specific adjunctive marker for thalamic glioma. We further demonstrated that maximal surgical resection confers a survival benefit and intraoperative mTV serves as a standardized treatment workflow to optimize care for thalamic glioma.

Association measurements, such as mutual information (MI), are fundamental in the analysis of cancer multi-omics data for identifying cancer-related genes, gene signatures, and gene regulatory networks, thereby shedding light on tumor development, progression, and treatment. Confounding factors, including tumor purity and mutation burden, can bias association measurements in MI, potentially leading to the misclassification of passenger events as drivers. Conditional mutual information (CMI) provides a robust framework for assessing both linear and nonlinear associations while effectively accounting for different confounding factors. An R package called conMItion is introduced to estimate CMI and its statistical significance for multi-omics data, with the flexibility to adjust for one or two confounding factors. We demonstrated the utilization of conMItion through two use cases. First, we identified interchromosomal somatic copy number alteration-expression associations in bladder cancer. Second, we identified associated cell types within the lung cancer tumor microenvironment using single-cell RNA sequencing datasets.

APOBEC mutational signatures represent a robust predictive biomarker for ICI response in TMB-low metastatic NSCLC, identifying responders particularly among PD-L1-negative patients where biomarker guidance is most needed, detectable from targeted gene panels used in routine clinical practice.

It should be differentiated from other tumors with similar morphology, particularly intestinal-type and non-intestinal adenocarcinomas as well as yolk sac tumors. To avoid misdiagnosis, SMARCB1 immunohistochemistry should be routinely applied in the diagnosis and differential diagnosis of high-grade sinonasal malignant tumors.

These findings demonstrate that genomic alteration status, including TP53 functional subclassification, provides clinically meaningful information beyond transcriptional profiling alone, supporting integrative genomics and transcriptomics analysis for precision oncology in rare cancers.