The somatic mutation profile of the tumors indicated that that loss of heterozygosity (LOH) at the <i>TP53</i> gene might have occurred during the differentiation of the founder clone into NEC, while a <i>SMAD4</i> mutation might have contributed to SCC development, indicating branching and subclonal evolution from common founder clone to both NEC and SCC. The gene discussed is SMAD4; the disease is neuroendocrine carcinoma.