The genomic landscape of small cell carcinoma of the esophagus

Small cell carcinoma of the esophagus (SCCE) is the most common extrapulmonary small cell carcinoma, accounting for 1%–2.8% of all esophageal carcinomas. 1 Most patients with SCCE die within 2 years of diagnosis and experience a median survival of only 8–13 months. 1 Due to lack of prospective data and its similarities in histological appearance and clinical behavior to small cell lung cancer (SCLC), treatments for SCCE are adopted from well-established therapeutic strategies for SCLC. 2 Chemotherapy is initially effective for SCCE, but most patients suffer a rapid recurrence and die within a few months. 2 More effective and precise treatment strategies for SCCE are urgently required, but have been hampered by lack of information on the molecular drivers of this deadly cancer. 3 Genome sequencing studies have revealed several potential driver events in two other major subtypes of esophageal carcinoma, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), and showed that they have distinct molecular characteristics, indicating the heterogeneity of esophageal carcinomas. 4 , 5 To understand the genetic basis of this deadly disease and enable the development of new diagnostic and therapeutic tools for its treatment, we performed genomic profiling of 55 patients with SCCE using whole-exome sequencing (WES) validated by ultra-deep targeted sequencing and copy number microarray assays.