SCLC and NSCLC are both associated with smoking and developed after p16 loss providing evidence that p16 functions to suppress tumorigenesis through RB1 independent mechanisms in epithelial cell lineages that give rise to both neuroendocrine and non-neuroendocrine cancers.13, 47, 48 Although p16 loss is not detected in human SCLC, these studies indicate that mechanisms underlying p16-dependent protection against DNA damage and carcinogenesis are shared in epithelial cells that give rise to both NSCLC and SCLC. The gene discussed is RB1; the disease is neuroendocrine carcinoma.