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Integrated genomic characterization of oesophageal carcinoma

Cancer Genome Atlas Research Network

Nature. 2017 Jan 12;541(7636):169-175.

ABSTRACT

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.

Comment in: Cancer genomics: Spot the difference. [Nature. 2017]

PMID: 28052061

DOI: 10.1038/nature20805

Commentary by Prof Lordick and Dr Elizabeth Smyth

Oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC) share an anatomic location but have distinct risk factors and epidemiology, and patients with either histology are frequently treated with identical chemotherapy, chemoradiotherapy and surgical approaches. The Cancer Genome Atlas (TCGA) publication on oesophageal cancer provides empirical evidence of the key differences between oesophageal OSCC) and OAC (REF). Using multiplatform analysis techniques, the TCGA authors demonstrate that OSCC tumours are more similar to squamous cell carcinoma of the head and neck than to OAC, whereas OAC tumours are molecularly indistinguishable from the chromosomally unstable (CIN) group of gastric cancers identified in the previous gastric cancer TCGA report. These findings suggest that in future, treatment approaches for OSCC and OAC might diverge from the current common approach; this will also be important to consider when designing future clinical trials. 

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