The genomic landscape of small cell carcinoma of the esophagus


Small cell carcinoma of the oesophagus (SCCE) is a deadly malignancy, while its genetic characteristic remains unknown and treatment is commonly adopted from therapies for its histologically identical counterpart, small cell lung cancer (SCLC). We performed whole-exome sequencing to examine the genetic landscape of 55 patients with SCCE. We identified three novel significantly mutated genes (PDE3A, PTPRM and CBLN2) and mutations in other five well-known tumour-associated genes (TP53, RB1, NOTCH1, FAT1 and FBXW7). Notably, activation of Wnt signaling pathway including DVL3 amplification were ubiquitously observed. Furthermore, comparison analysis revealed that SCCE tumours were more closely related to oesophageal squamous cell carcinoma, other than esophagus adenocarcinoma and SCLC, suggesting that current therapies for SCCE might be inappropriate. Functional characterizations suggested that PDE3A acts as a novel onocogene. Moreover, pathway enrichment analysis revealed that genes involved in cell cycle, p53, Notch and Wnt signaling were frequently altered in SCCE. Our findings provide insights for better understanding of SCCE pathogenesis and better treatment strategies for patients with SCCE.

Cell research