Integrated genomic characterization of oesophageal carcinoma

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.

A Pan-Cancer Compendium of Genes Deregulated by Somatic Genomic Rearrangement across More Than 1,400 Cases

“…WGS profiling and SV calling was carried for individual TCGA projects as previously described (Cancer Genome Atlas Network, 2012, 2015a, 2015b; Cancer Genome Atlas Research Network, 2014a, 2014b, 2015a, 2015b, 2017a, 2017b; Cancer Genome Atlas Research Network et al, 2013a; Chen et al, 2016; Davis et al, 2014; Robertson et al, 2017), as well as detailed in the Supplemental Experimental Procedures. Previous studies show that on the order of 96%–98% of high-confidence SVs from high-pass WGS data detected by the Meerkat algorithm are able to be validated by PCR (Davis et al, 2014; Yang et al, 2013).…”

“…With TCGA gene expression data, large-scale integration between WGS and expression data is possible. TCGA WGS data were generated with either low-depth-of-coverage (low pass) or high-depth-of-coverage (high pass), with both types of WGS being used effectively to identify SVs in previous TCGA consortium-led studies focusing on a specific cancer type (Cancer Genome Atlas Network, 2012, 2015a, 2015b; Cancer Genome Atlas Research Network, 2013, 2014a, 2014b, 2015b, 2017a, 2017b; Davis et al, 2014; Robertson et al, 2017). While low-pass WGS may involve decreased sensitivity of detection, >1,200 cases in TCGA have low-pass data, representing a rich resource, with no pan-cancer study to date using these data.…”

Krüppel-Like Factor 7 is a Marker of Aggressive Gastric Cancer and Poor Prognosis

“…High-throughput RNA sequencing techniques have been widely used to identify reliable molecular biomarkers that may serve as new predictors or therapeutic targets. The TCGA database is a large-scale genomic database that primarily reports somatic changes of cancers including GC [21, 22]. The final goal of these tremendous efforts is to tailor patient treatment in a personalized manner and drive customization of disease care by implementing genetic tumor information.…”

Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications

“…Adenocarcinoma of the distal esophagus predominates in the West, whereas squamous cell carcinoma, which tends to localize in the middle thoracic esophagus, predominates in the East. Molecular features also differ between adenocarcinoma and squamous cell carcinoma; for example, 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 3. Traditionally, both adenocarcinomas and squamous cell tumors have been treated by surgical resection 4.…”