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

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  • Jean Charles Nault

    (Inserm, UMR-674, Génomique fonctionnelle des tumeurs solides, IUH
    Faculté de Médecine, Labex Immuno-oncology, Université Paris Descartes, Sorbonne Paris Cité)

  • Maxime Mallet

    (Inserm, UMR-674, Génomique fonctionnelle des tumeurs solides, IUH
    Faculté de Médecine, Labex Immuno-oncology, Université Paris Descartes, Sorbonne Paris Cité)

  • Camilla Pilati

    (Inserm, UMR-674, Génomique fonctionnelle des tumeurs solides, IUH
    Faculté de Médecine, Labex Immuno-oncology, Université Paris Descartes, Sorbonne Paris Cité)

  • Julien Calderaro

    (Inserm, UMR-674, Génomique fonctionnelle des tumeurs solides, IUH
    Faculté de Médecine, Labex Immuno-oncology, Université Paris Descartes, Sorbonne Paris Cité
    Assistance Publique-Hôpitaux de Paris, CHU Henri Mondor)

  • Paulette Bioulac-Sage

    (Inserm, UMR-1053, Université Victor Segalen Bordeaux 2
    CHU de Bordeaux, Pellegrin Hospital)

  • Christophe Laurent

    (CHU de Bordeaux, Pellegrin Hospital)

  • Alexis Laurent

    (Assistance Publique-Hôpitaux de Paris, digestive, CHU Henri Mondor
    Inserm, U955)

  • Daniel Cherqui

    (Assistance Publique-Hôpitaux de Paris, digestive, CHU Henri Mondor
    Assistance Publique-Hôpitaux de Paris, Hopital Paul Brousse)

  • Charles Balabaud

    (Inserm, UMR-1053, Université Victor Segalen Bordeaux 2)

  • Jessica Zucman-Rossi

    (Inserm, UMR-674, Génomique fonctionnelle des tumeurs solides, IUH
    Faculté de Médecine, Labex Immuno-oncology, Université Paris Descartes, Sorbonne Paris Cité
    Assistance Publique-Hôpitaux de Paris, Hopital Europeen Georges Pompidou)

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.

Suggested Citation

  • Jean Charles Nault & Maxime Mallet & Camilla Pilati & Julien Calderaro & Paulette Bioulac-Sage & Christophe Laurent & Alexis Laurent & Daniel Cherqui & Charles Balabaud & Jessica Zucman-Rossi, 2013. "High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions," Nature Communications, Nature, vol. 4(1), pages 1-7, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3218
    DOI: 10.1038/ncomms3218
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    Cited by:

    1. Jill Pilet & Theo Z. Hirsch & Barkha Gupta & Amélie Roehrig & Guillaume Morcrette & Aurore Pire & Eric Letouzé & Brice Fresneau & Sophie Taque & Laurence Brugières & Sophie Branchereau & Christophe Ch, 2023. "Preneoplastic liver colonization by 11p15.5 altered mosaic cells in young children with hepatoblastoma," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Siddharth Narayanan & Marion Dubarry & Conor Lawless & A Peter Banks & Darren J Wilkinson & Simon K Whitehall & David Lydall, 2015. "Quantitative Fitness Analysis Identifies exo1∆ and Other Suppressors or Enhancers of Telomere Defects in Schizosaccharomyces pombe," PLOS ONE, Public Library of Science, vol. 10(7), pages 1-15, July.

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