title: High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions.
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.
authors.affiliation: Inserm, UMR-674, Génomique fonctionnelle des tumeurs solides, IUH, Paris F-75010, France.
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Nault
authors.forename: Maxime
authors.initials: M
authors.lastname: Mallet
authors.forename: Camilla
authors.initials: C
authors.lastname: Pilati
authors.forename: Julien
authors.initials: J
authors.lastname: Calderaro
authors.forename: Paulette
authors.initials: P
authors.lastname: Bioulac-Sage
authors.forename: Christophe
authors.initials: C
authors.lastname: Laurent
authors.forename: Alexis
authors.initials: A
authors.lastname: Laurent
authors.forename: Daniel
authors.initials: D
authors.lastname: Cherqui
authors.forename: Charles
authors.initials: C
authors.lastname: Balabaud
authors.forename: Jessica
authors.initials: J
authors.lastname: Zucman-Rossi
authors.forename: Jessica
authors.initials: J
authors.lastname: Zucman Rossi
mesh_terms: D018248:Adenoma, Liver Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D012333:RNA, Messenger; D051176:beta Catenin; C509186:TERT protein, human; D019098:Telomerase