(See sections titled “Endogenous sources of mutation and their signatures” and “Connections between epigenetic dysregulation and relapse in DLBCL.”) They also point toward genes whose products directly modify chromatin, such as EZH2. Eventually, chronic epigenetic disruption leads to an initiating genetic mutation that formally drives oncogenesis, followed by further genetic and epigenetic aberrations. The gene discussed is EZH2; the disease is diffuse large B-cell lymphoma.