Classification of tumors using whole-genome methylation profiling

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The classification of Central Nervous System (CNS) tumors is undergoing a significant transformation, driven by the adoption of biologically grounded, objective diagnostic tools. A major shift began with the 2016 WHO update, which formally introduced molecular features, such as specific genetic alterations, into the diagnostic definitions of tumor entities. Building on this, the 2021 WHO classification now includes several tumor types that can only be accurately defined using DNA methylation profiling, underscoring its essential role in modern neuropathology. DNA methylation analysis has emerged as a powerful modality, offering high-resolution tumor classification with improved diagnostic accuracy, reproducibility, and reliability. In real-world clinical practice, application of methylation-based classification has led to diagnostic revisions in approximately 12% of brain tumor cases, often resulting in significant changes in patient management. When integrated with next-generation sequencing (NGS) approaches, capturing both DNA mutations and RNA gene fusions, this framework delivers an unprecedented level of diagnostic precision. Together with standard histopathology and clinical context, this comprehensive molecular strategy supports the development of a state-of-the-art precision diagnostics platform in neuro-oncology. This project directly aligns with the strategic goals of the National Cancer Institute (NCI), particularly in advancing early and accurate cancer detection, developing effective diagnostic and therapeutic approaches, eliminating disparities in care, and maximizing the utility of cancer data. By contributing to innovation, enhancing diagnostic workflows, and fostering interdisciplinary collaboration, this initiative also supports NCI's mission to reduce the burden of cancer and accelerate progress across the cancer research continuum.