SCLC tumor mutational profiling reveals a clear smoking signature, providing direct evidence that tobacco carcinogens are responsible for the initiation of SCLC, Concomitant inactivation of two tumor suppressors, i.e., p53 and RB (encoded by TP53 and RB1, respectively) is found in most SCLC cases. The gene discussed is RB1; the disease is neoplasm.