Abstract
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.
Highlights
Esophageal cancer is the sixth most common cause of cancer death worldwide, and its incidence has increased in recent years
In light of the lack of the said research, we evaluated the somatic mutations and copy-number variants in 42 T1 or High-grade intraepithelial neoplasia (IN) (HGIN) patients to study the genetic changes in the early-stage development of Esophageal SCC (ESCC)
Some papers reported that the pathological transitions from dysplasia to ESCC occur via the accumulation of genetic changes [14, 16]
Summary
Esophageal cancer is the sixth most common cause of cancer death worldwide, and its incidence has increased in recent years. There are two general types of esophageal cancer: squamous cell carcinoma (SCC) and adenocarcinoma. Esophageal SCC (ESCC) is the most common type of esophageal cancer in Asian countries, accounting for approximately 80% of esophageal cancer cases [1]. The most common cause of ESCC is damage to the esophageal mucosa by chronic inflammation due to exposure to acetaldehyde or other such carcinogens [2]. Somatic mutations and copy-number variants (CNVs) have been implicated in the development and proliferation of ESCC [4,5,6]. Liu et al reported mutations and gene copy-number changes in non-tumor, IN, and ESCC samples, collected from 70 advancedESCC patients [14]. This paper shows a panorama of the genetic architecture of the carcinogenesis process in www.oncotarget.com
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