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Genetics of hepatocellular tumors

Oncogene volume 25, pages 3778–3786 (2006)Cite this article

Abstract

Numerous genetic alterations are accumulated during the process of hepatocarcinogenesis. These genetic alterations can be divided into two groups. The first set of genetic alterations is specific of hepatocellular tumor risk factors. It includes integration of hepatitis B virus (HBV) DNA, R249S TP53 (tumor protein p53) mutation in aflatoxin B1-exposed patients, KRAS mutations related to vinyl chloride exposure, hepatocyte nuclear factor 1α (HNF1α) mutations associated to hepatocellular adenomas and adenomatosis polyposis coli (APC) germline mutations predisposing to hepatoblastomas. The second set of genetic alterations are etiological nonspecific, it includes recurrent gains and losses of chromosomes, alteration of TP53 gene, activation of WNT/β-catenin pathway through CTNNB1/β-catenin and AXIN (axis inhibition protein) mutations, inactivation of retinoblastoma and IGF2R (insulin-like growth factor 2 receptor) pathways through inactivation of RB1 (retinoblastoma 1), P16 and IGF2R. Comprehensive analyses of these genetic alterations have defined two pathways of hepatocarcinogenesis according to the presence or the absence of chromosomal instability. Hepatitis B virus and poorly differentiated tumors are related to chromosome instable tumors associated with frequent TP53 mutations, whereas non-HBV and well-differentiated tumors are related to chromosomal stable samples that are frequently β-catenin activated. These classifications have clinical relevance as genetic alterations may also be related to prognosis.

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Acknowledgements

This work was supported by the Inserm and the Fondation de France.

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  1. Inserm, U775, Bases Moléculaires de la réponse aux xénobiotiques, Paris, France

    P Laurent-Puig

  2. Université Paris 5, Paris, France

    P Laurent-Puig

  3. Inserm, U674, Génomique fonctionnelle des tumeurs solides, Paris, France

    J Zucman-Rossi

  4. Université Paris 7 Denis Diderot, Institut Universitaire d'Hématologie, CEPH, Paris, France

    J Zucman-Rossi

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Laurent-Puig, P., Zucman-Rossi, J. Genetics of hepatocellular tumors. Oncogene 25, 3778–3786 (2006). https://doi.org/10.1038/sj.onc.1209547

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