High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions

Jean Charles Nault, Maxime Mallet, Camilla Pilati, Julien Calderaro, Paulette Bioulac-Sage, Christophe Laurent, Alexis Laurent, Daniel Cherqui, Charles Balabaud and Jessica Zucman-Rossi ()
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Jean Charles Nault: Inserm, UMR-674, Génomique fonctionnelle des tumeurs solides, IUH
Maxime Mallet: Inserm, UMR-674, Génomique fonctionnelle des tumeurs solides, IUH
Camilla Pilati: Inserm, UMR-674, Génomique fonctionnelle des tumeurs solides, IUH
Julien Calderaro: Inserm, UMR-674, Génomique fonctionnelle des tumeurs solides, IUH
Paulette Bioulac-Sage: Inserm, UMR-1053, Université Victor Segalen Bordeaux 2
Christophe Laurent: CHU de Bordeaux, Pellegrin Hospital
Alexis Laurent: Assistance Publique-Hôpitaux de Paris, digestive, CHU Henri Mondor
Daniel Cherqui: Assistance Publique-Hôpitaux de Paris, digestive, CHU Henri Mondor
Charles Balabaud: Inserm, UMR-1053, Université Victor Segalen Bordeaux 2
Jessica Zucman-Rossi: Inserm, UMR-674, Génomique fonctionnelle des tumeurs solides, IUH

Nature Communications, 2013, vol. 4, issue 1, 1-7

Abstract: Abstract Somatic mutations activating telomerase reverse-trancriptase promoter were recently identified in several tumour types. Here we identify frequent similar mutations in human hepatocellular carcinomas (59%), cirrhotic preneoplastic macronodules (25%) and hepatocellular adenomas with malignant transformation in hepatocellular carcinomas (44%). In hepatocellular tumours, telomerase reverse-transcripase- and CTNNB1-activating mutations are significantly associated. Moreover, preliminary data suggest that telomerase reverse-trancriptase promoter mutations can increase the expression of telomerase transcript. In conclusion, telomerase reverse-trancriptase promoter mutation is the earliest recurrent genetic event identified in cirrhotic preneoplastic lesions so far and is also the most frequent genetic alteration in hepatocellular carcinomas, arising from both the cirrhotic or non-cirrhotic liver.

Date: 2013
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DOI: 10.1038/ncomms3218

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