Nature. 2017 Jan 12;541(7636):169-175. doi: 10.1038/nature20805. Epub 2017 Jan 4.
Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.
食管癌在全球范围内都很突出；然而，针对这些癌症的靶向治疗很少，其生存率仍然很低。在此，我们对来自西方和东方人群的164例食管癌进行了全面的分子分析。除了已知的组织病理学和流行病学差异外，分子特征还区分了食管鳞状细胞癌和食管腺癌。食管鳞状细胞癌与其他器官的鳞状细胞癌的相似性超过了与食管腺癌的相似性。我们的分析确定了食管鳞状细胞癌的三个分子亚类，但没有一个显示出人类乳头瘤病毒的病因学作用的证据。鳞状细胞癌显示出CCND1和SOX2和/或TP63的频繁基因组扩增，而ERBB2、VEGFA以及GATA4和GATA6在腺癌中更常发生扩增。食管腺癌与胃腺癌的染色体不稳定变体非常相似，这表明这些癌症可被视为单一疾病实体。然而，包括DNA高甲基化在内的一些分子特征在食管腺癌中出现的比例过高。这些数据为促进对这些肿瘤进行更合理的分类提供了框架，并为新疗法奠定了基础。
