Besides that, another study [24] suggested an alternative pathway for SCLC where it may originate from non-neuroendocrine cancer stem cells that acquire neuroendocrine differentiation through inactivating NOTCH (neurogenic locus notch homolog) mutations, ASCL1 (Achaete-scute homolog 1) overexpression and additionally a bi-allelic loss of TP53 and RB1. This evidence concerns the gene RB1 and small cell lung carcinoma.