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

// Yuji Urabe 1 , Kenichi Kagemoto 2 , C. Nelson Hayes 2 , Koki Nakamura 2 , Kazuhiko Masuda 2 , Atsushi Ono 2 , Shinji Tanaka 3 , Koji Arihiro 4 and Kazuaki Chayama 2 1 Division of Regeneration and Medicine Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan 2 Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan 3 Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan 4 Department of Pathology, Hiroshima University Hospital, Hiroshima, Japan Correspondence to: Kazuaki Chayama, email: chayama@mba.ocn.ne.jp Keywords: early-stage esophageal squamous cell carcinoma; exome sequencing; target sequencing; genomic characterization; TP53 Received: August 26, 2018     Accepted: May 26, 2019     Published: June 25, 2019 ABSTRACT Major risk factors for esophageal squamous cell carcinoma (ESCC) are smoking, alcohol consumption, and single nucleotide polymorphisms in ADH1Band ALDH2. 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 sequencingof 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 TP53 and NOTCH1 , CDKN2Adeletions, and CCND1 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 TP53 , NOTCH1 , CDKN2A, and CCND1 , are the key changes that promote the transformation of esophageal mucosa to ESCC.