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DNA Methylation Profiling: An Emerging Paradigm for Cancer Diagnosis.

Histomorphology has been a mainstay of cancer diagnosis in anatomic pathology for many years. DNA methylation profiling is an additional emerging tool that will serve as an adjunct to increase accuracy of pathological diagnosis. Genome-wide interrogation of DNA methylation signatures, in conjunction with machine learning methods, has allowed for the creation of clinical-grade classifiers, most prominently in central nervous system and soft tissue tumors. Tumor DNA methylation profiling has led to the identification of new entities and the consolidation of morphologically disparate cancers into biologically coherent entities, and it will progressively become mainstream in the future. In addition, DNA methylation patterns in circulating tumor DNA hold great promise for minimally invasive cancer detection and classification. Despite practical challenges that accompany any new technology, methylation profiling is here to stay and will become increasingly utilized as a cancer diagnostic tool across a range of tumor types. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.