Brägelmann J, Ponce CB, Marcelain K, et al. - This study was undertaken to explore the epigenetic changes along the model of gallbladder cancer (GBC) carcinogenesis represented by the sequence gallstone disease → dysplasia → GBC in Chile, the country with the highest incidence of GBC worldwide. Researchers examined genomic DNA extracted from sections of formalin-fixed, paraffin-embedded gallbladder tissue using Illumina Infinium MethylationEPIC BeadChips to perform epigenome-wide methylation profiling. The outcomes demonstrate that GBC carcinogenesis comprises three main methylation stages: early (gallstone disease and low-grade dysplasia), intermediate (high-grade dysplasia), and late (GBC). This study’s findings demonstrate that the distinguished gradual changes in methylation and copy number variations, may help to enhance the understanding of the mechanisms underlying this aggressive disease and eventually lead to improved treatment and early diagnosis of GBC.