Epigenetic mechanisms and the hallmarks of cancer: an intimate affair

Epigenetic mechanisms comprising DNA methylation, histone modifications, and noncoding RNAs affect chromatin structure and regulate gene expression. These mechanisms control normal embryonic development and adult life and their deregulation contributes to several diseases including cancer. The process of tumorigenesis is complex and results from the evolution of different hallmarks of cancer. Hanahan and Weinberg presented in 2000 and 2011 seminal contributions in the cancer field, first the six hallmarks of cancer and a decade later two additional hallmarks and two enabling characteristics were added. Here, we surmise that epigenetic mechanisms regulate and contribute to every single hallmark in cancer, and thus represent the hallmark of hallmarks in tumorigenesis. Focusing on epigenetics as a major hallmark in cancer formation has profound preventive, therapeutic, and clinical implications.