Epigenetic changes are present in all human cancers and cooperate with genetic alterations to drive the cancer phenotype. These changes involve DNA methylation, histone modifiers, chromatin remodelers, microRNAs, and other chromatin components. Cancer genetics and epigenetics are closely linked, with epigenetic changes causing mutations in genes and mutations frequently observed in genes that modify the epigenome. Epigenetic therapies, which aim to reverse these changes, are now a standard of care for preleukemic disorders and certain lymphomas. Their application in solid tumors is also emerging as a viable therapeutic approach. The article discusses the biological basis of cancer, the importance of chromatin to cancer, the role of DNA methylation, hypermethylated gene promoters, the importance of epigenetic gene silencing in early tumor progression, the molecular anatomy of epigenetically silenced cancer genes, and the summary of major research issues in understanding epigenetic gene silencing. It also covers DNA methylation abnormalities as biomarkers for cancer detection and monitoring prognosis, and epigenetic therapy. Cancer arises from the somatically heritable deregulation of genes controlling cell division, death, and movement. Tumor-suppressor genes (TSGs) can be inactivated through mutations, loss of heterozygosity, or epigenetic silencing. Epigenetic silencing can occur through deregulation of epigenetic machinery, inappropriate methylation of cytosine residues, changes in histone posttranslational modifications, and alterations in nucleosome-remodeling or histone exchange complexes. Changes in regulatory microRNA expression patterns are also noted. Epigenetic mechanisms are a third pathway in cancer development, and their molecular mechanisms are well understood. Epigenetic silencing has significant implications for cancer prevention, detection, and therapy. FDA-approved drugs reverse epigenetic changes and restore gene activity in cancer cells. DNA methylation changes can be detected with high sensitivity, enabling early cancer detection. The biological basis of cancer involves gene expression dysregulation, with key cellular pathways disrupted in human cancers. Genetic and epigenetic mechanisms contribute to these disruptions. Epigenetic alterations include abnormal DNA methylation, disrupted histone posttranslational modifications, and changes in chromatin composition and organization. These changes are linked to altered gene expression and chromatin structure, affecting cancer progression. DNA methylation plays a critical role in cancer, with hypomethylation and hypermethylation contributing to oncogenesis. Hypomethylation leads to genomic instability and aneuploidy, while hypermethylation silences tumor suppressor genes. DNA hypomethylation is associated with increased mutation rates and aneuploidy, and can activate transcription of repeats, transposable elements, and oncogenes. DNA hypermethylation in cancer-related gene promoters leads to gene silencing and inactivation of tumor suppressor genes. DNA methylation abnormalities are significant biomarkers for cancer detection andEpigenetic changes are present in all human cancers and cooperate with genetic alterations to drive the cancer phenotype. These changes involve DNA methylation, histone modifiers, chromatin remodelers, microRNAs, and other chromatin components. Cancer genetics and epigenetics are closely linked, with epigenetic changes causing mutations in genes and mutations frequently observed in genes that modify the epigenome. Epigenetic therapies, which aim to reverse these changes, are now a standard of care for preleukemic disorders and certain lymphomas. Their application in solid tumors is also emerging as a viable therapeutic approach. The article discusses the biological basis of cancer, the importance of chromatin to cancer, the role of DNA methylation, hypermethylated gene promoters, the importance of epigenetic gene silencing in early tumor progression, the molecular anatomy of epigenetically silenced cancer genes, and the summary of major research issues in understanding epigenetic gene silencing. It also covers DNA methylation abnormalities as biomarkers for cancer detection and monitoring prognosis, and epigenetic therapy. Cancer arises from the somatically heritable deregulation of genes controlling cell division, death, and movement. Tumor-suppressor genes (TSGs) can be inactivated through mutations, loss of heterozygosity, or epigenetic silencing. Epigenetic silencing can occur through deregulation of epigenetic machinery, inappropriate methylation of cytosine residues, changes in histone posttranslational modifications, and alterations in nucleosome-remodeling or histone exchange complexes. Changes in regulatory microRNA expression patterns are also noted. Epigenetic mechanisms are a third pathway in cancer development, and their molecular mechanisms are well understood. Epigenetic silencing has significant implications for cancer prevention, detection, and therapy. FDA-approved drugs reverse epigenetic changes and restore gene activity in cancer cells. DNA methylation changes can be detected with high sensitivity, enabling early cancer detection. The biological basis of cancer involves gene expression dysregulation, with key cellular pathways disrupted in human cancers. Genetic and epigenetic mechanisms contribute to these disruptions. Epigenetic alterations include abnormal DNA methylation, disrupted histone posttranslational modifications, and changes in chromatin composition and organization. These changes are linked to altered gene expression and chromatin structure, affecting cancer progression. DNA methylation plays a critical role in cancer, with hypomethylation and hypermethylation contributing to oncogenesis. Hypomethylation leads to genomic instability and aneuploidy, while hypermethylation silences tumor suppressor genes. DNA hypomethylation is associated with increased mutation rates and aneuploidy, and can activate transcription of repeats, transposable elements, and oncogenes. DNA hypermethylation in cancer-related gene promoters leads to gene silencing and inactivation of tumor suppressor genes. DNA methylation abnormalities are significant biomarkers for cancer detection and