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Profil moléculaire des tumeurs hépatobiliaires: vers de nouvelles pistes, facteurs prédictifs et cibles thérapeutiques

Molecular profiling of hepatobiliary cancers: new runways, predictive factors and therapeutic targets

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Oncologie

Abstract

The improvement in the knowledge of the pathways involved in cancerogenesis has led to the development of original targeted therapies that are being evaluated in recent clinical trials applied to hepatobiliary cancers. Primary hepatobiliary cancers, like other cancers, are considered somatic genetic diseases whose a mapping of the genetic defects will be available at the whole genome scale. Using genetic anomalies as markers is still an emerging approach but is promising to decipher the heterogeneity of the hepatobiliary cancers to classify them at themolecular scale, refine the prognosis and offer a personalized treatment.

Résumé

La description des voies de signalisation de la cancérogenèse est le fondement des nouvelles stratégies de thérapies ciblées qui sont en cours d’évaluation dans les cancers hépatobiliaires. Les cancers hépatobiliaires primitifs, comme les autres cancers, sont considérés comme des maladies génétiques somatiques dont la cartographie des anomalies génétiques à l’échelle du génome sera bientôt disponible. L’utilisation de marqueurs génétiques des tumeurs est une approche émergente pour tenter d’identifier, à l’échelle moléculaire, leur hétérogénéité pour classifier les tumeurs hépatobiliaires, évaluer le pronostic ou proposer un traitement personnalisé.

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Références

  1. Abou-Alfa GK, Schwartz L, Ricci S, et al. (2006) Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol (Official Journal of the American Society of Clinical Oncology) 24: 4293–4300

    Article  CAS  Google Scholar 

  2. Ahrendt SA, Rashid A, Chow JT, et al. (2000) P53 overexpression and KRAS gene mutations in primary sclerosing cholangitis-associated biliary tract cancer. J Hepatobiliary Pancreat Surg 7: 426–431

    Article  PubMed  CAS  Google Scholar 

  3. Audard V, Grimber G, Elie C, et al. (2007) Cholestasis is a marker for hepatocellular carcinomas displaying beta-catenin mutations. J Pathol 212: 345–322

    Article  PubMed  CAS  Google Scholar 

  4. Boyault S, Rickman DS, de Reyniès A, et al. (2007) Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology (Baltimore, MD) 45: 42–52

    Article  CAS  Google Scholar 

  5. Briggs CD, Neal CP, Mann CD, et al. (2009) Prognostic molecular markers in cholangiocarcinoma: a systematic review. Eur J Cancer (Oxford, England: 1990) 45: 33–47

    Article  CAS  Google Scholar 

  6. Budhu A, Jia HL, Forgues M, et al. (2008) Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology (Baltimore, MD) 47: 897–907

    Article  CAS  Google Scholar 

  7. Chiappini F, Gross-Goupil M, Saffroy R, et al. (2004) Microsatellite instability mutator phenotype in hepatocellular carcinoma in non-alcoholic and non-virally infected normal livers. Carcinogenesis 25: 541–547

    Article  PubMed  CAS  Google Scholar 

  8. Ding X, Yang LY, Huang GW, et al. (2005) Role of AFP mRNA expression in peripheral blood as a predictor for postsurgical recurrence of hepatocellular carcinoma: a systematic review and meta-analysis. World J Gastroenterol 11: 2656–2661

    PubMed  CAS  Google Scholar 

  9. Fava G, Lorenzini I (2012) Molecular pathogenesis of cholangiocarcinoma. Int J Hepatol 2012: 630543

    PubMed  CAS  Google Scholar 

  10. Gruenberger B, Schueller J, Heubrandtner U, et al. (2010) Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study. Lancet Oncol 11: 1142–1148

    Article  PubMed  CAS  Google Scholar 

  11. Gwak GY, Yoon JH, Shin CM, et al. (2005) Detection of response-predicting mutations in the kinase domain of the epidermal growth factor receptor gene in cholangiocarcinomas. J Cancer Res Clin Oncol 131: 649–652

    Article  PubMed  CAS  Google Scholar 

  12. He B, Qiu X, Li P, et al. (2010) HCCNet: an integrated network database of hepatocellular carcinoma. Cell Research 20: 732–734

    Article  PubMed  Google Scholar 

  13. Hoshida Y, Villanueva A, Kobayashi M, et al. (2008) Gene expression in fixed tissues and outcome in hepatocellular carcinoma. New En J Med 359: 1995–2004

    Article  CAS  Google Scholar 

  14. Hsu HC, Jeng YM, Mao TL, et al. (2000) Beta-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis. Am J Pathol 157: 763–770

    Article  PubMed  CAS  Google Scholar 

  15. Hussain SP, Schwank J, Staib F, et al. (2007) TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. Oncogene 26: 2166–2176

    Article  PubMed  CAS  Google Scholar 

  16. Isa T, Tomita S, Nakachi A, et al. (2002) Analysis of microsatellite instability, KRAS gene mutation and P53 protein overexpression in intrahepatic cholangiocarcinoma. Hepatogastroenterology 49: 604–608

    PubMed  CAS  Google Scholar 

  17. Ji J, Shi J, Budhu A, et al. (2009) MicroRNA expression, survival, and response to interferon in liver cancer. New Eng J Medicine 361: 1437–447

    Article  CAS  Google Scholar 

  18. Karapetis CS, Khambata-Ford S, Jonker DJ, et al. (2008) KRAS mutations and benefit from cetuximab in advanced colorectal cancer. New Eng J Med 359: 1757–1765

    Article  PubMed  CAS  Google Scholar 

  19. Katoh H, Shibata T, Kokubu A, et al. (2005) Genetic profile of hepatocellular carcinoma revealed by array-based comparative genomic hybridization: identification of genetic indicators to predict patient outcome. J Hepatol 43: 863–874

    Article  PubMed  CAS  Google Scholar 

  20. Koga Y, Kitajima Y, Miyoshi A, et al. (2005) Tumor progression through epigenetic gene silencing of O(6)-methylguanine-DNA methyltransferase in human biliary tract cancers. Ann Surg Oncol 12: 354–363

    Article  PubMed  Google Scholar 

  21. Leone F, Cavalloni G, Pignochino Y, et al. (2006) Somatic mutations of epidermal growth factor receptor in bile duct and gallbladder carcinoma. Clin Cancer Res (An Official Journal of the American Association for Cancer Research) 12: 1680–1685

    Article  CAS  Google Scholar 

  22. Llovet JM, Ricci S, Mazzaferro V, et al. (2008) Sorafenib in advanced hepatocellular carcinoma. New Eng J Med 359: 378–390

    Article  PubMed  CAS  Google Scholar 

  23. Lynch TJ, Bell DW, Sordella R, et al. (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. New Eng J Med 350: 2129–2139

    Article  PubMed  CAS  Google Scholar 

  24. Miki D, Ochi H, Hayes CN, et al. (2011) Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers. Nat Genet 43: 797–800

    Article  PubMed  CAS  Google Scholar 

  25. Mitsudomi T, Hamajima N, Ogawa M, et al. (2000) Prognostic significance of P53 alterations in patients with non-small cell lung cancer: a meta-analysis. Clin Cancer Res (An Official Journal of the American Association for Cancer Research) 6: 4055–4063

    CAS  Google Scholar 

  26. Miura N, Maeda Y, Kanbe T, et al. (2005) Serum human telomerase reverse transcriptase messenger RNA as a novel tumor marker for hepatocellular carcinoma. Clin Cancer Res (An Official Journal of the American Association for Cancer Research) 11: 3205–3209

    Article  CAS  Google Scholar 

  27. Monaco AP (2009) The role of mTor inhibitors in the management of posttransplant malignancy. Transplantation 87: 157–163

    Article  PubMed  CAS  Google Scholar 

  28. Nault JC, Zucman-Rossi J (2011) Genetics of hepatobiliary carcinogenesis. Semin Liver Dis 31: 173–187

    Article  PubMed  CAS  Google Scholar 

  29. Ohashi K, Nakajima Y, Kanehiro H, et al. (1995) Ki-ras mutations and P53 protein expressions in intrahepatic cholangiocarcinomas: relation to gross tumor morphology. Gastroenterology 109: 1612–1617

    Article  PubMed  CAS  Google Scholar 

  30. Patel T (2002) Worldwide trends in mortality from biliary tract malignancies. BMC Cancer 2: 10

    Article  PubMed  Google Scholar 

  31. Totoki Y, Tatsuno K, Yamamoto S, et al. (2011) High-resolution characterization of a hepatocellular carcinoma genome. Nat Genet 43: 464–469

    Article  PubMed  CAS  Google Scholar 

  32. Villanueva A, Hoshida Y, Battiston C, et al. (2011) Combining clinical, pathology, and gene expression data to predict recurrence of hepatocellular carcinoma. Gastroenterology 140: 1501–12.e2

    Article  PubMed  CAS  Google Scholar 

  33. Villanueva A, Newell P, Chiang DY, et al. (2007) Genomics and signaling pathways in hepatocellular carcinoma. Semin Liver Dis 27: 55–76

    Article  PubMed  CAS  Google Scholar 

  34. Wiedmann MW, Mössner J (2010) Molecular targeted therapy of biliary tract cancer-results of the first clinical studies. Curr Drug Targets 11: 834–850

    Article  PubMed  CAS  Google Scholar 

  35. Woo HG, Wang XW, Budhu A, et al. (2011) Association of TP53 mutations with stem cell-like gene expression and survival of patients with hepatocellular carcinoma. Gastroenterology 140: 1063–1070

    Article  PubMed  CAS  Google Scholar 

  36. Yu XJ, Fang F, Tang CL, et al. (2011) dbHCCvar: a comprehensive database of human genetic variations in hepatocellular carcinoma. Hum Mutat 32(12): E2316

    Article  Google Scholar 

  37. Zucman-Rossi J, Benhamouche S, Godard C, et al. (2007) Differential effects of inactivated Axin1 and activated beta-catenin mutations in human hepatocellular carcinomas. Oncogene 26: 774–780

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. UMR 1078 Brest, faculté de médecine et des sciences de la santé, université de Brest, F-29200, Brest, France

    P. Guéguen & C. Le Maréchal

  2. Inserm, U1078, Brest, F-29200, France

    P. Guéguen & C. Le Maréchal

  3. laboratoire de génétique moléculaire et d’histocompatibilité, CHRU Brest, F-29220, Brest, France

    P. Guéguen & C. Le Maréchal

  4. Université européenne de Bretagne, F-35000, Rennes, France

    P. Guéguen & C. Le Maréchal

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  1. P. Guéguen
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Correspondence to C. Le Maréchal.

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Guéguen, P., Le Maréchal, C. Profil moléculaire des tumeurs hépatobiliaires: vers de nouvelles pistes, facteurs prédictifs et cibles thérapeutiques. Oncologie 14, 186–190 (2012). https://doi.org/10.1007/s10269-012-2138-9

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  • DOI: https://doi.org/10.1007/s10269-012-2138-9

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