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Gut 63:709-710 doi:10.1136/gutjnl-2013-305334
  • Commentary

Editing liver tumours

  1. Puri Fortes3
  1. 1 Institut Cochin, Université Paris-Descartes, Centre National de la Recherche Scientifique (CNRS), UMR 8104, Paris, France
  2. 2 Institut National de la Santé et de la Recherche Médicale (INSERM) U1016, Paris, France
  3. 3 Department of Gene Therapy and Hepatology, Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain
  1. Correspondence to Dr Puri Fortes, Department of Hepatology and Gene Therapy, Foundation for Applied Medical Research, University of Navarra. Avda, Pío XII 55, Pamplona 31008, Spain; pfortes{at}unav.es and Dr Sabine Colnot, Institut Cochin, INSERM U1016, 24, rue du Faubourg Saint Jacques, Paris 75014, France; sabine.colnot{at}inserm.fr
  • Received 27 June 2013
  • Accepted 28 June 2013
  • Published Online First 22 July 2013

There is an urgent need for new therapeutic options for hepatocellular carcinoma (HCC), which is currently the third cause of cancer-related death worldwide.1 HCC develops most frequently in the setting of cirrhosis. This premalignant condition occurs as a consequence of chronic liver disease, mainly as a result of hepatitis B and C viral infection, alcohol abuse and obesity. The poor efficacy of many antiproliferative agents against HCC is due in part to the inefficient drug delivery and metabolism in cirrhotic livers, leading to unbearable drug toxicity. Novel therapies for HCC could be developed after the identification of oncogenic addiction loops or primary ‘gatekeeper’ and ‘driver’ mutations that would allow for HCC initiation and progression, respectively.

To this end, previous large-scale studies in HCC have focused on searching for DNA mutations and transcriptome alterations. This allowed the classification of HCCs with DNA mutations that affect different pathways, that is, β-catenin signalling, P53/cell cycle control, chromatin remodelling and/or PI3K/Ras cascade.2 However, no driver DNA mutations have been identified for at least 20% HCCs,2 suggesting that other mutator or driver events could occur. To search for such alternative events, new genome-wide studies should be performed to analyse whether the transcriptome modification caused by changes in alternative splicing, alternative polyadenylation or RNA editing could have an impact on hepatocarcinogenesis.

RNA editing has now entered the limelight in HCC thanks to the study of Chan and colleagues,3 which positions RNA editing as a generator of tumour-specific transcriptome …

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