| GeneLibs

题目:: Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets.
作者:: Schulze(Kornelius),Imbeaud(Sandrine),Letouzé(Eric),Alexandrov(Ludmil B),Calderaro(Julien),Rebouissou(Sandra),Couchy(Gabrielle),Meiller(Clément),Shinde(Jayendra),Soysouvanh(Frederic),Calatayud(Anna-Line),Pinyol(Roser),Pelletier(Laura),Balabaud(Charles),Laurent(Alexis),Blanc(Jean-Frederic),Mazzaferro(Vincenzo),Calvo(Fabien),Villanueva(Augusto),Nault(Jean-Charles),Bioulac-Sage(Paulette),Stratton(Michael R),Llovet(Josep M),Zucman-Rossi(Jessica)
状态:: 发布时间2015-04-28 , 更新时间 2016-11-22
期刊:: Nat Genet
摘要:: 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 Food and Drug Administration (FDA)-approved drugs. In conclusion, we identified risk factor-specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.
语言:: eng
DOI:

文献库文献相关信息

DataTable pData

联系方式

微信公众号

文献库 文献相关信息

DataTable pData

联系方式

微信公众号

文献库文献相关信息