Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma.

Nature Genetics
Cécile GuichardJessica Zucman-Rossi

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Here, we performed high-resolution copy-number analysis on 125 HCC tumors and whole-exome sequencing on 24 of these tumors. We identified 135 homozygous deletions and 994 somatic mutations of genes with predicted functional consequences. We found new recurrent alterations in four genes (ARID1A, RPS6KA3, NFE2L2 and IRF2) not previously described in HCC. Functional analyses showed tumor suppressor properties for IRF2, whose inactivation, exclusively found in hepatitis B virus (HBV)-related tumors, led to impaired TP53 function. In contrast, inactivation of chromatin remodelers was frequent and predominant in alcohol-related tumors. Moreover, association of mutations in specific genes (RPS6KA3-AXIN1 and NFE2L2-CTNNB1) suggested that Wnt/β-catenin signaling might cooperate in liver carcinogenesis with both oxidative stress metabolism and Ras/mitogen-activated protein kinase (MAPK) pathways. This study provides insight into the somatic mutational landscape in HCC and identifies interactions between mutations in oncogene and tumor suppressor gene mutations related to specific risk factors.

References

Jul 24, 1997·Oncogene·E Douville, J Downward
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Oct 2, 2002·Nature Genetics·Olivier BluteauJessica Zucman-Rossi
Dec 26, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sandrine BoyaultJessica Zucman-Rossi
Mar 9, 2007·Nature·Christopher GreenmanMichael R Stratton
Jun 16, 2007·Gastroenterology·Hashem B El-Serag, K Lenhard Rudolph
Sep 6, 2007·Genome Research·Sorin DraghiciRoberto Romero
Feb 29, 2008·Annual Review of Immunology·Tomohiko TamuraTadatsugu Taniguchi
Jun 3, 2008·Biochemical and Biophysical Research Communications·Ke-Jun HanHong-Bing Shu
Sep 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Tatsuhiro ShibataSetsuo Hirohashi
Nov 27, 2008·The Biochemical Journal·Susanne PetterssonKathryn L Ball
Dec 8, 2009·The Journal of Pathology·Yoo Ri KimSug Hyung Lee
Feb 19, 2010·Nature·Rameen BeroukhimMatthew Meyerson
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Oct 15, 2010·The New England Journal of Medicine·Kimberly C WiegandDavid G Huntsman
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Feb 26, 2011·International Journal of Cancer. Journal International Du Cancer·Jacques FerlayDonald Maxwell Parkin
Apr 19, 2011·Nature Genetics·Yasushi TotokiTatsuhiro Shibata
May 4, 2011·Seminars in Liver Disease·Jean-Charles Nault, Jessica Zucman-Rossi
Jun 10, 2011·Nature Reviews. Cancer·Boris G Wilson, Charles W M Roberts
Jul 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yong TaoChung-I Wu
Aug 16, 2011·Journal of Neurochemistry·Anne SchneiderAndré Hanauer
Oct 20, 2011·Human Mutation·Siân JonesNickolas Papadopoulos

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Citations

Nov 30, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Dandan YuDengfu Yao
Jul 9, 2013·Mutation Research·Olga KalininaPascal Pineau
Oct 4, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Henryk DudekBob D Brown
Sep 27, 2012·Nature Genetics·Zemin Zhang
Jun 26, 2013·Nature Genetics·Yusuke SatoSeishi Ogawa
Oct 15, 2013·Nature Genetics·Cristina Balbás-MartínezFrancisco X Real
Aug 31, 2013·Nature Reviews. Drug Discovery·Claudio HetzHeather P Harding
Sep 12, 2013·Nature Reviews. Genetics·Ian R WatsonLynda Chin
Mar 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Patrick J KillelaHai Yan
Sep 26, 2012·Pathology International·Tatsuhiro Shibata
Jul 3, 2013·Oxidative Medicine and Cellular Longevity·Eri KobayashiMasayuki Yamamoto
Dec 5, 2012·Cancer Discovery·Jennifer N Wu, Charles W M Roberts
May 3, 2013·The Journal of Clinical Investigation·Taro Yamashita, Xin Wei Wang
Feb 26, 2014·BMC Systems Biology·Hui YuZhongming Zhao
May 8, 2013·PloS One·Cristina Balbás-MartínezFrancisco X Real
Sep 17, 2013·International Journal of Molecular Sciences·Eleftherios P SamartzisPatrick Imesch
Jan 1, 2014·World Journal of Gastroenterology : WJG·De-Leung GuChian-Feng Chen
Apr 4, 2014·World Journal of Gastroenterology : WJG·Stephen L Chan, Winnie Yeo
Feb 4, 2014·Genome Medicine·Lisa EversMichael T Barrett
Nov 28, 2013·Virchows Archiv : an International Journal of Pathology·Julien CalderaroJessica Zucman-Rossi
Jan 8, 2014·Nature Reviews. Clinical Oncology·Augusto Villanueva, Josep M Llovet
Mar 13, 2014·Database : the Journal of Biological Databases and Curation·Omer AnFrancesca D Ciccarelli
Jan 25, 2014·Trends in Molecular Medicine·Nicolas DejeansEric Chevet
May 29, 2014·International Journal of Hepatology·Cheng Ji
Jul 22, 2014·Gastroenterology·Tom LueddeRobert F Schwabe
May 20, 2014·Current Treatment Options in Oncology·Anuj Patel, Weijing Sun

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