Genomic characterization of early-stage esophageal squamous cell carcinoma in a Japanese population
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Yuji Urabe1, Kenichi Kagemoto2, C. Nelson Hayes2, Koki Nakamura2, Kazuhiko Masuda2, Atsushi Ono2, Shinji Tanaka3, Koji Arihiro4 and Kazuaki Chayama2
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
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
Major risk factors for esophageal squamous cell carcinoma (ESCC) are smoking, alcohol consumption, and single nucleotide polymorphisms in ADH1B and 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 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 TP53 and NOTCH1, CDKN2A deletions, 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.
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