Integrated genomic characterization of oesophageal carcinoma

Jihun Kim, Reanne Bowlby, Andrew J. Mungall, A. Gordon Robertson, Robert D. Odze, Andrew D. Cherniack, Juliann Shih, Chandra Sekhar Pedamallu, Carrie Cibulskis, Andrew Dunford, Samuel R. Meier, Jaegil Kim, J. Raphael, Hsin Ta Wu, Alexandra M. Wong, Joseph E. Willis, Adam J. Bass (Lead / Corresponding author), Sarah Derks, Katherine Garman, Shannon J. McCallMacIej Wiznerowicz, Angeliki Pantazi, Michael Parfenov, Vésteinn Thorsson, Ilya Shmulevich, Varsha Dhankani, Michael Miller, Ku Leuven Ryo Sakai, Kenneth Wang, Nikolaus Schultz, Ronglai Shen, Arshi Arora, Nils Weinhold, Francisco Sánchez-Vega, David P. Kelsen, Julia Zhang, Ina Felau, John Demchok, Charles S. Rabkin, M. Constanza Camargo, Jean Claude Zenklusen, Jay Bowen, Kristen Leraas, Tara M. Lichtenberg, Christina Curtis, Jose A. Seoane, Akinyemi I. Ojesina, David G. Beer, Frank Carey, Ian Forgie, The Cancer Genome Atlas Research Network

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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.

Original languageEnglish
Pages (from-to)169-174
Number of pages6
JournalNature
Volume541
Issue number7636
Early online date4 Jan 2017
DOIs
Publication statusPublished - 12 Jan 2017

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    Kim, J., Bowlby, R., Mungall, A. J., Robertson, A. G., Odze, R. D., Cherniack, A. D., Shih, J., Pedamallu, C. S., Cibulskis, C., Dunford, A., Meier, S. R., Kim, J., Raphael, J., Wu, H. T., Wong, A. M., Willis, J. E., Bass, A. J., Derks, S., Garman, K., ... The Cancer Genome Atlas Research Network (2017). Integrated genomic characterization of oesophageal carcinoma. Nature, 541(7636), 169-174. https://doi.org/10.1038/nature20805