Abstract IA007: DNA methylation in cancer: From knowledge to applications

Abstract For the last thirty years an increasing amount of evidence has shown the relevance of epigenetics in cell biology and tissue physiology, being DNA methylation aberrations in cancer the flag-ship for the recognition of its disturbance in human diseases. From the candidate gene approaches, new powerful technologies such as comprehensive DNA methylation microarrays and whole genome bisulfite sequencing has recently emerged that have reinforced the notion of epigenetic disruption in the crossroad of many sickness. From the poster-boy case of MGMT hypermethylation in the prediction of alkylating drug response to the personalized treatment of leukemia with small molecules targeted to fusion proteins involving histone modifiers, the field has walked a long path. The current talk will focus in the epigenetic profiling, basically at the level of DNA methylation and histone modifications, that is starting to provide clinical value in the diagnosis, prognosis and prediction of response to drug therapies. For cancer, we have already a wide view of the undergoing DNA methylation events that expand beyond classical promoter CpG islands of tumor suppressor genes and we have a growing list of mutated chromatin remodeler genes that contributes to the tumorigenesis process. It is time to apply this knowledge in practical clinical situations like the diagnosis of cancers of unknown primary, the screening of malignancies in high-risk populations or a biomarker selection of the patients that should receive treatment with anticancer drugs, including immunotherapy. Beyond cancer, DNA methylation is starting to be recognized as playing a major role in infectious diseases, and in this regard, the present lecture will also address the epigenomic component of COVID-19. Most important, Epigenomics can be added to Genomics, Transcriptomics and Proteomics plus Bioinformatics to create a Multomics view of human diseases. Citation Format: Manel Esteller. DNA methylation in cancer: From knowledge to applications [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Methylation, Clonal Hematopoiesis, and Cancer; 2025 Feb 1-4; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2025;85(3 Suppl):Abstract nr IA007