Many mechanisms have been proposed to explain H19's role in tumor initiation and progression, including inhibition of the tumor suppressor retinoblastoma Rb through H19-encoded miR-675;26, 27 alteration of gene transcription via interaction with Polycomb repressive complex 2 components;28 and sequestration and inhibition of the tumor suppressor microRNA let-7.5, 11 Our studies suggest that another mechanism of H19-mediated carcinogenesis may also be at play: genome-wide dysregulation of gene methylation. The gene discussed is H19; the disease is neoplasm.