Figure 2.

Tumor heterogeneity in SCLC with regard to neuroendocrine differentiation, molecular subtypes, and gene expression profile

Neuroendocrine (NE) differentiation can be defined by the expression pattern of different NE markers, including chromogranin A, synaptophysin, neural cell adhesion molecule 1, and gastrin-releasing peptide. However, a minority of SCLCs are negative for all standard NE markers. Additionally, SCLC can be subclassified according to the relative expression of four key transcriptional regulators: achaete-scute homolog 1 (ASCL1; also known as ASH1), neurogenic differentiation factor 1 (NEUROD1), yes-associated protein 1 (YAP1), and POU class 2 homeobox 3 (POU2F3). Various genetic alterations, biological properties, and thus potential therapeutic vulnerabilities are associated with these molecular subsets.