Recent updates of genetic and genomic alterations in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide. However, the molecular mechanisms underlining the development and progression of HCC remain unclear. Genetic and genomic alterations are common events in various types of cancers including HCC. With the development and application of next generation sequencing technology, novel genetic and genomic alterations in HCC have been identified. Here, the article reviews recent updates on the genetic and genomic alterations in HCC.

Keywords

Hepatocellular carcinoma / genetics / genomics / next generation sequencing

References

[1] Theise ND,Kew MC.Liver cancer.In: Stewart B, Wild C, editors. World Cancer Report 2014.2014;LyonInternational Agency for Research on Cancer577-93

[2] Kan Z,Liu X,Barber TD,Gao H,Willard MD,Hauptschein R,Fernandez J,Zhang Q,Chen R,Lee NP,Lin Z,Yi K,Li L,Yang J,Ju J,Estrella H,Wei P,Wulur IH,Ehsani ME,Loboda A,Aggarwal A,Fan ST,Hardwick J,Dai H,Luk JM.Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma..Genome Res2013;23:1422-33 PMCID:PMC3759719

[3] Miyoshi Y,Nagasawa Y,Sasaki Y,Murata M,Nakamura Y.Activation of the beta-catenin gene in primary hepatocellular carcinomas by somatic alterations involving exon 3..Cancer Res1998;58:2524-7

[4] Li M,Zhang X,Anders RA,Pawlik TM,Kannangai R,Velculescu VE,Zhou S,Hruban RH,Cai J,Kinzler KW.Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma..Nat Genet2011;43:828-9 PMCID:PMC3163746

[5] Yakicier MC,Romano A,Ozturk M.Smad2 and Smad4 gene mutations in hepatocellular carcinoma..Oncogene1999;18:4879-83

[6] Soung YH,Kim SY,Park WS,Kim SH,Yoo NJ.Caspase-8 gene is frequently inactivated by the frameshift somatic mutation 1225_1226delTG in hepatocellular carcinomas..Oncogene2005;24:141-7

[7] Kremer-Tal S,Narla G,Schwartz M,Katz A,Bioulac-Sage P,Friedman SL.Frequent inactivation of the tumor suppressor Kruppel-like factor 6 (KLF6) in hepatocellular carcinoma..Hepatology2004;40:1047-52

[8] Malkin D,Strong LC,Nelson CE,Kassel J,Bischoff FZ,Friend SH.Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms..Science1990;250:1233-8

[9] Hussain SP,Staib F,Harris CC.TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer..Oncogene2007;26:2166-76

[10] Petitjean A,Kato S,Tavtigian SV,Olivier M.Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database..Hum Mutat2007;28:622-9

[11] Guichard C,Imbeaud S,Pelletier L,Calderaro J,Letexier M,Clément B,Chevet E,Couchy G,Calvo F.Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma..Nat Genet.2012;44:694-8

[12] Whittaker S,Zhu AX.The role of signaling pathways in the development and treatment of hepatocellular carcinoma..Oncogene2010;29:4989-5005

[13] Huang J,Wang Q,Dai JH,Zhu ZD,Liu XY,Fei QL,Cai B,Xiao HS,Han ZG.Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma..Nat Genet.2012;44:1117-21

[14] Fujimoto A,Abe T,Hosoda F,Aoki M,Kubo M,Arai Y,Shirakihara T,Shibuya T,Watanabe-Makino K,Nakamura H,Ojima H,Okusaka T,Shigekawa Y,Arihiro K,Gotoh K,Ariizumi S,Yamada T,Kosuge T,Kamatani N,Nakagama H,Tsunoda T,Nakagawa H.Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators..Nat Genet2012;44:760-4

[15] Xie HJ,Noh JH,Kim JK,Ryu JC,Kim SY,Yoo NJ,Park WS.Mutational analysis of JAK1 gene in human hepatocellular carcinoma..Neoplasma2009;56:136-40

[16] Negrini S,Halazonetis TD.Genomic instability - an evolving hallmark of cancer..Nat Rev Mol Cell Biol2010;11:220-8

[17] Bunz F,Speicher MR,Sedivy JM,Vogelstein B.Targeted inactivation of p53 in human cells does not result in aneuploidy..Cancer Res2002;62:1129-33

[18] Gorgoulis VG,Karakaidos P,Kotsinas A,Venere M,Kastrinakis NG,Kletsas D,Herlyn M,Halazonetis TD.Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions..Nature2005;434:907-13

[19] Bartkova J,Koed K,Tort F,Guldberg P,Nesland JM,Ørntoft T,Bartek J.DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis..Nature2005;434:864-70

[20] Wang Y,Li M,Zhao YP,Li Q,Tong WM,Huang J.Mutation inactivation of Nijmegen breakage syndrome gene (NBS1) in hepatocellular carcinoma and intrahepatic cholangiocarcinoma..PLoS One2013;8:e82426 PMCID:PMC3862623

[21] Miki D,Hayes CN,Yoshima T,Ikeda K,Toyota J,Tsunoda T,Nakamura Y,Chayama K.Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers..Nat Genet2011;43:797-800

[22] Zhang H,Hu Z,Qian J,Ma F,Yu L,Wang Z,Zhang Y,Wei Z,Xie W,Yu X,Xia X,Yang H,Yang J,Chen M,Lin D,He F.Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers..Nat Genet2010;42:755-8

[23] Liang KH,Yeh CT.GALNT14 SNP as a potential predictor of response to combination chemotherapy using 5-FU, mitoxantrone and cisplatin in advanced HCC..Pharmacogenomics2011;12:1061-73

[24] Yeh CT,Lin CC,Hsu CL.A single nucleotide polymorphism on the GALNT14 gene as an effective predictor of response to chemotherapy in advanced hepatocellular carcinoma..Int J Cancer2014;134:1214-24

[25] Guo X,Ma X,Shang Y,Yang H,Xing J.A meta-analysis of array-CGH studies implicates antiviral immunity pathways in the development of hepatocellular carcinoma..PLoS One2011;6:e28404 PMCID:PMC3236189

[26] Tomlinson IP,Roylance RR.Loss of heterozygosity analysis: practically and conceptually flawed?.Genes Chromosomes Cancer2002;34:349-53

[27] Lau SH.Cytogenetic and molecular genetic alterations in hepatocellular carcinoma..Acta Pharmacol Sin.2005;26:659-65

[28] Niketeghad F,Caselmann WH,Geissler F,Schirmacher P.Frequent genomic imbalances suggest commonly altered tumour genes in human hepatocarcinogenesis..Br J Cancer2001;85:697-704 PMCID:PMC2364116

[29] Rashid A,Qian GS,Hamilton SR.Genetic alterations in hepatocellular carcinomas: association between loss of chromosome 4q and p53 gene mutations..Br J Cancer1999;80:59-66 PMCID:PMC2362990

[30] Zondervan PE,Alers JC,Schalm SW,van Dekken H.Molecular cytogenetic evaluation of virus-associated and non-viral hepatocellular carcinoma: analysis of 26 carcinomas and 12 concurrent dysplasias..J Pathol2000;192:207-15

[31] Laurent-Puig P,Bluteau O,Franco D,Monges G,Bioulac-Sage P.Genetic alterations associated with hepatocellular carcinomas define distinct path-ways of hepatocarcinogenesis..Gastroenterology2001;120:1763-73

[32] Zhang H,Wang Q,Weng D,Zhou J,Sun J,Liang X,Pan K,Xia J.Analysis of loss of heterozygosity on chromosome 4q in hepatocellular carcinoma using high-throughput SNP array..Oncol Rep2010;23:445-55

[33] Peng C,Wu J,Tang J,Zhou L.A critical role for ZDHHC2 in metastasis and recurrence in human hepatocellular carcinoma..Biomed Res Int2014;2014:832712

[34] Yasui K,Gen Y,Dohi O,Kitaichi T,Iwai N,Yamaguchi K,Sumida Y,Tanaka S,Itoh Y.EVI1, a target gene for amplification at 3q26, antagonizes transforming growth factor-β-mediated growth inhibition in hepatocellular carcinoma..Cancer Sci2015;106:929-37 PMCID:PMC4520646

[35] Yung MK,Yip CW,Tong CY,Cheung TT,So S,Cheung ST.Copy number gain of granulin-epithelin precursor (GEP) at chromosome 17q21 associates with overexpression in human liver cancer..BMC Cancer2015;15:264 PMCID:PMC4403714

[36] Slamon D,Robert N,Martin M,Mackey J,Chan A,Pinter T,Liu MC,von Minckwitz G,Bee V,Bendahmane B,Lindsay MA,Crown J.Adjuvant trastuzumab in HER2-positive breast cancer..N Engl J Med2011;365:1273-83 PMCID:PMC3268553

[37] Bacaksiz A,Bilezikci B.Determination of HER-2/ Neu status in hepatocellular carcinoma cases..Genet Test2008;12:211-4

[38] Panvichian R,Angkathunyakul N.TOP2A amplification and overexpression in hepatocellular carcinoma tissues..Biomed Res Int2015;2015:381602

[39] Giefing M,Brauze D,Luczak M,Pelinska K,Tönnies H,Figlerowicz M,Szyfter K.High resolution ArrayCGH and expression profiling identifies PTPRD and PCDH17/ PCH68 as tumor suppressor gene candidates in laryngeal squamous cell carcinoma..Genes Chromosomes Cancer2011;50:154-66

[40] Nalesnik MA,Ding Y,Zheng ZL,Marsh JW,Luo JH.Gene deletions and amplifications in human hepatocellular carcinomas: correlation with hepatocyte growth regulation..Am J Pathol2012;180:1495-508 PMCID:PMC3657620

[41] Kohno T,Girard L,Iwakawa R,Sanchez-Cespedes M,Yokota J.A catalog of genes homozygously deleted in human lung cancer and the candidacy of PTPRD as a tumor suppressor gene..Genes Chromosomes Cancer2010;49:342-52 PMCID:PMC2921682

[42] Acun T,Oztas E,Yakicier MC.PTPRD is homozygously deleted and epigenetically downregulated in human hepatocellular carcinomas..OMICS2015;19:220-9