Genomic characterization of early-stage esophageal squamous cell carcinoma in a Japanese population

Abstract

Major risk factors for esophageal squamous cell carcinoma (ESCC) are smoking, alcohol consumption, and single nucleotide polymorphisms in <i>ADH1B</i> and <i>ALDH2</i>. Several groups have reported large-scale genomic analyses of ESCCs. However, the specific genetic changes that promote the development of ESCC have not been characterized. We performed exome sequencing of 16 fresh esophageal squamous cell neoplasms and targeted sequencing of 128 genes in 52 archival specimens, of which 26 were cancerous, and 26 were adjacent normal tissue, from Japanese ESCC patients. We found significantly more somatic mutations in <i>TP53</i> and <i>NOTCH1</i>, <i>CDKN2A</i> deletions, and <i>CCND1</i> amplifications in cancerous areas than in non-cancerous areas, consistent with previous studies that have characterized them as tumor suppressors and oncogenes. These data suggest that mutations, deletions, and amplifications, which alter the function of <i>TP53</i>, <i>NOTCH1</i>, <i>CDKN2A</i>, and <i>CCND1</i>, are the key changes that promote the transformation of esophageal mucosa to ESCC.