1. Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis
- Author
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Arun J. Sanyal, Claudia P. Oliveira, Andrew V. Uzilov, Beatriz Minguez, Huan Wang, Suzanne Faure-Dupuy, Sara Torrecilla, Helen L. Reeves, Jean-François Dufour, Mathias Heikenwalder, Carmen Andreu-Oller, Flair José Carrilho, Charissa Chang, Catherine E. Willoughby, Marta Piqué-Gili, Scott L. Friedman, Leow Wei-Qiang, Svenja Schuehle, Judit Peix, Carla Montironi, Paolo Boffetta, Josep M. Llovet, Stephanie Roessler, Roser Pinyol, Peter Schirmacher, Miguel Torres-Martin, Patricia Taik, Venancio Avancini Ferreira Alves, Youngmin A. Lee, Tobias Riedl, Pierluigi Ramadori, Daniela Sia, Agrin Moeini, Anja Lachenmayer, Swan N. Thung, Pinyol R., Torrecilla S., Wang H., Montironi C., Pique-Gili M., Torres-Martin M., Wei-Qiang L., Willoughby C.E., Ramadori P., Andreu-Oller C., Taik P., Lee Y.A., Moeini A., Peix J., Faure-Dupuy S., Riedl T., Schuehle S., Oliveira C.P., Alves V.A., Boffetta P., Lachenmayer A., Roessler S., Minguez B., Schirmacher P., Dufour J.-F., Thung S.N., Reeves H.L., Carrilho F.J., Chang C., Uzilov A.V., Heikenwalder M., Sanyal A., Friedman S.L., Sia D., and Llovet J.M.
- Subjects
0301 basic medicine ,Male ,obesity ,Síndrome metabòlica ,Subclass ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Risk Factors ,Molecular models ,Exome sequencing ,Aged, 80 and over ,Liver Neoplasms ,Animal models in research ,mutational signature ,Middle Aged ,Metabolic syndrome ,Liver Neoplasm ,Hepatocellular carcinoma ,Obesitat ,030211 gastroenterology & hepatology ,Female ,Liver cancer ,Human ,Carcinoma, Hepatocellular ,Biology ,digestive system ,metabolic syndrome ,Models moleculars ,liver cancer ,Càncer de fetge ,03 medical and health sciences ,medicine ,Humans ,Obesity ,molecular cla ,neoplasms ,Molecular Biology ,Aged ,Hepatology ,animal model ,Mutació (Biologia) ,Cancer ,nutritional and metabolic diseases ,HCCS ,Mutation (Biology) ,medicine.disease ,digestive system diseases ,030104 developmental biology ,Cancer research ,Steatohepatitis ,Models animals en la investigació ,610 Medizin und Gesundheit ,ACVR2A - Abstract
BACKGROUND AND AIMS Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing globally, but its molecular features are not well defined. We aimed to identify unique molecular traits characterising NASH-HCC compared to other HCC aetiologies. METHODS We collected 80 NASH-HCC and 125 NASH samples from 5 institutions. Expression array (n = 53 NASH-HCC; n = 74 NASH) and whole exome sequencing (n = 52 NASH-HCC) data were compared to HCCs of other aetiologies (n = 184). Three NASH-HCC mouse models were analysed by RNA-seq/expression-array (n = 20). Activin A receptor type 2A (ACVR2A) was silenced in HCC cells and proliferation assessed by colorimetric and colony formation assays. RESULTS Mutational profiling of NASH-HCC tumours revealed TERT promoter (56%), CTNNB1 (28%), TP53 (18%) and ACVR2A (10%) as the most frequently mutated genes. ACVR2A mutation rates were higher in NASH-HCC than in other HCC aetiologies (10% vs. 3%, p
- Published
- 2020