Authors
Kornelius Schulze, Sandrine Imbeaud, Eric Letouzé, Ludmil B Alexandrov, Julien Calderaro, Sandra Rebouissou, Gabrielle Couchy, Clément Meiller, Jayendra Shinde, Frederic Soysouvanh, Anna-Line Calatayud, Roser Pinyol, Laura Pelletier, Charles Balabaud, Alexis Laurent, Jean-Frederic Blanc, Vincenzo Mazzaferro, Fabien Calvo, Augusto Villanueva, Jean-Charles Nault, Paulette Bioulac-Sage, Michael R Stratton, Josep M Llovet, Jessica Zucman-Rossi
Publication date
2015/5
Journal
Nature genetics
Volume
47
Issue
5
Pages
505-511
Publisher
Nature Publishing Group US
Description
Genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. Analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereas FGF3, FGF4, FGF19 or CCND1 amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US …
Scholar articles
K Schulze, S Imbeaud, E Letouzé, LB Alexandrov… - Nature genetics, 2015