Small cell carcinomas of the bladder and lung are characterized by a convergent but distinct pathogenesis. Small cell carcinomas of the bladder and lung are characterized by a convergent but distinct pathogenesis

Small cell carcinoma of the bladder (SCCB) is a rare and aggressive neuroendocrine tumor with a dismal prognosis and limited treatment options. As SCCB is histologically indistinguishable from small cell lung cancer, a shared pathogenesis and cell of origin has been proposed. The aim of this study is to determine whether SCCBs arise from a pre-existent urothelial carcinoma or share a molecular pathogenesis in common with small cell lung cancer. Results We performed an integrative analysis of 61 SCCB tumors to identify histology- and organ-specific similarities and differences. SCCB has a high somatic mutational burden driven predominantly by an APOBEC-mediated mutational process. TP53, RB1, and TERT promoter mutations were present in nearly all samples. While these events appeared to arise early in all affected tumors and likely reflect an evolutionary branch point that may have driven small cell lineage differentiation, they were unlikely the founding... (for more see dbGaP study page.)