It has been proposed that NEstem, a specific subgroup of PNECs, could be the primary originators of SCLC initiation is thought to stem from the immediate and sustained activation of NEstem cell renewal after the loss of Rb and p53.This loss might render NEstem cells unresponsive to signals that typically trigger their dispersal or revert them to a non-cancerous state, potentially explaining the propensity of SCLC for early metastatic spread. The gene discussed is TP53; the disease is small cell lung carcinoma.