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系統識別號 U0026-0802201114065600
論文名稱(中文) 利用微衛星不穩定性分析技術分析B型肝炎病毒所引起肝癌之毛玻璃狀肝細胞
論文名稱(英文) Microsatellite Instability Analysis of the Ground Glass Hepatocytes in Hepatitis B virus-related Hepatoma
校院名稱 成功大學
系所名稱(中) 醫學檢驗生物技術學系碩博士班
系所名稱(英) Department of Medical Laboratory Science and Biotechnology
學年度 99
學期 1
出版年 100
研究生(中文) 阮玉鴛兒
研究生(英文) Nguyen Ngoc Uyen Nhi
學號 T36987017
學位類別 碩士
語文別 英文
論文頁數 88頁
口試委員 召集委員-蘇益仁
口試委員-王慧菁
指導教授-黃溫雅
中文關鍵字 none 
英文關鍵字 HBV  MSI  pre-S2 mutant LHBs  in vitro binding assay 
學科別分類
中文摘要 none
英文摘要 ABSTRACT
Keywords: HBS, MSI, pre-S2 mutant LHBs, in vitro binding assay
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer death worldwide. Chronic infection of hepatitis B virus (HBV) is associated with the majority of HCC. However, the genetic events of hepatocarcinogenesis are relatively poorly understood. The pre-S1 and pre-S2 partially deleted large HBV surface proteins (LHBs), called pre-S1 and pre-S2 mutant LHBS (∆1, ∆2LHBs), are highly associated with HBV-induced HCC and are found in type I and type II ground glass hepatocytes (GGHs), respectively. These proteins accumulate in endoplasmic reticulum (ER) to induce strong ER stress, oxidative DNA damage and genomic instability. To observe the genomic alterations in clinical HCC samples, we performed microsatellite instability (MSI) analysis. We collected liver sections from 15 [13 HBV(+), 2 HCV(+)] HCC patients that received liver surgery at NCKU. The liver tissues were undergone HE and IHC staining for HBs. The tumor, GGH and normal liver parts were separately collected. Genomic DNA from each liver part as well as the corresponding peripheral blood was extracted and applied to microsatellite instability tests. Five fluorescence-labeled mononucleotide repeat MSI markers NR-21, BAT-26, BAT-25, NR-24, and MONO-27 and two pentanucleotide repeat markers Penta C and Penta D were co-amplified by multiplex PCR. The PCR products were analyzed using the Genescan analysis. Nine of the 13 HBV-positive HCC tissues displayed GGH morphology whereas the other 4 did not. For each patient, the MS patterns in the peripheral blood, normal liver, GGH, and tumorous sections were analyzed then compared with each other. The results of MSI study showed that 2 of the 13 (15.4%) HBV-positive HCC cases showed minor MSI in tumorous and GGH sections; whereas none of the non-HBV(+) cases showed MSI. In summary, some GGH, which expresses the pre-S mutant LHBS, presents minor MSI, the most sensitive biomarker for genomic instability.


論文目次 TABLE OF CONTENTS
ABSTRACT I
TABLE OF CONTENTS II
LIST OF TABLES V
LIST OF FIGURES VI
LIST OF SUPPLEMENTARY TABLES VII
LIST OF SUPPLEMENTARY FIGURES VIII
LIST OF APPENDICES IX
LIST OF ABBREVIATIONS AND SYMBOLS X
1 INTRODUCTION 1
1.1 Hepatitis B virus biology 1
1.1.1 Hepatitis B virus and hepatitis B 1
1.1.2 HBV serotypes 1
1.1.3 HBV genotypes and subgenotypes 2
1.1.4 Virion structure 3
1.1.5 Genome organization and viral proteins 3
1.1.6 Entry and replication 5
1.1.7 Transmission 6
1.1.8 Vaccination 7
1.2 Clinicopathological features of HBV infection. 7
1.2.1 Epidemiology 7
1.2.2 Chronic HBV infection 8
1.2.3 Hepatocellular carcinoma (malignant hepatoma) 9
1.2.4 Diagnosis and treatment of HBV infection 9
1.3 Molecular pathogenesis of Hepatitis B-induced hepatocarcinogenesis 10
1.3.1 HBV genome integrates into host chromosome 10
1.3.2 Role of HBx antigen (HBxAg) 10
1.3.3 HBV variants are associated with HCC. 11
1.3.4 Host factors correlated with HCC 12
1.3.5 Other HBV features (viral load, HBV genotypes) 12
1.4 Genetic alteration in hepatocarcinogenesis 13
1.5 Microsatellite instability 13
1.5.1 Microsatellite instability definition 13
1.5.2 Microsatellite instability in hepatocarcinogenesis 14
2 RESEARCH GOAL 15
3 MATERIALS AND METHODS 17
3.1 Patient tissues 17
3.2 DNA isolation 17
3.3 Multiplex PCR 18
3.4 Automated sequencing and data analysis 18
4 RESULTS 19
4.1 Clinicopathological features of hepatocellular carcinoma patients 19
4.2 HE and IHC staining for HBs showed the morphology of clinical liver tissues 19
4.3 15.4% HBV-positive HCC cases showed minor MSI in tumorous and GGH type II with 1bp shifted. 19
4.4 Pattern of microsatellites stable (MSS) 20
5 DISCUSSION 21
REFERENCES 24
6 SUPPLEMENTARY MATERIALS: VERIFICATION THE INTERACTION DOMAIN OF ∆2LHBS WITH JAB1 BY IN VITRO GST PULL-DOWN ASSAY 55
6.1 Suppl. Abstract 55
6.2 Suppl. Introduction: ∆2-LHBs – JAB1 interaction involved in hepatocarcinogenesis 56
6.2.1 Previous methods to determine protein-protein interactions 56
6.2.2 ∆2-LHBs – Jun activation domain-binding protein 1 (JAB1) interaction 57
6.2.3 Pre-S2 mutant LHBs – JAB1 interaction domain is on N-terminal amino acid residues 61-119 of Pre-S2 mutant LHBs. 57
6.3 Suppl. research aim: 58
6.4 Suppl. method: In vitro GST-pull-down assay 59
6.4.1 Construction of expression vectors (pre-S variants and JAB1) 59
6.4.2 Protein expression 61
6.4.3 Single step purification of pre-S2 variants using Ni-NTA beads 62
6.4.4 Single step purification of fusion GST-JAB1 constructs using GST beads 62
6.4.5 Determination of protein concentration 62
6.4.6 Protein electrophoresis (SDS-PAGE) 63
6.4.7 In vitro GST pull-down assay 63
6.4.8 Western blotting 63
6.5 Results 64
6.5.1 Generation of recombinant GST-tagged full-length JAB1 peptide 64
6.5.2 Generation of recombinant 6XHis-tagged N-terminus partially deleted of pre-S2 mutant LHBs 64
6.5.3 Functional characterization of the purified proteins showed by in vitro GST pull-down assay. 65
6.5.4 The N-terminus amino acid residue 61-119 of ∆2/pre-S binds to JAB1 as confirm by in vitro protein-protein interaction analysis. 65
6.6 Discussion 66
SUPPLEMENTARY REFERENCES 68
APPENDICES 78



LIST OF TABLES
Table 1: The 15 analyzed HCC patients for microsatellite instability 35




LIST OF FIGURES
Figure 1: HE and IHC staining for HBs showed the histological morphology in the livers of HBV-positive HCC patient S00390. 37
Figure 2: HE and IHC staining for HBs showed the histological morphology in the livers of HBV-positive HCC patient 0437. 38
Figure 3: HBV-negative HCC patient S00715 displays the pattern of microsatellites stable. 39
Figure 4 : HBV-positive HCC patient 0437 displays the pattern of minor microsatellites instability. 41
Figure 5: GGHs type II harboring the minor microsatellites instability in MONO-27 marker of two HBV-positive HCC patients. 42
Figure 6: The summary of MSI analysis results in this study 43
Figure 7: Pattern of MSI analysis from HBV-positive HCC patient 0117 44
Figure 8: Pattern of MSI analysis from HBV-positive HCC patient 0225 45
Figure 9: Pattern of MSI analysis from HBV-positive HCC patient 0956 46
Figure 10: Pattern of MSI analysis from HBV-positive HCC patient 1057 47
Figure 11 : Pattern of MSI analysis from HBV-positive HCC patient S00427 and S00587 48
Figure 12: Pattern of MSI analysis from HBV-positive HCC patient S00687 and S00338 49
Figure 13: Pattern of MSI analysis from HBV-positive HCC patient S0016 50
Figure 14: Pattern of MSI analysis from HBV-positive HCC patient S02112 51
Figure 15: Pattern of MSI analysis from HBV-positive HCC patient S00390 52
Figure 16: Pattern of MSI analysis from HBV-positive HCC patient S01189 53
Figure 17: Pattern of MSI analysis from non HBV-positive HCC patient S00696. 54


LIST OF SUPPLEMENTARY TABLES
Suppl. Table 1: Reagents 69
Suppl. Table 2: Buffers 71


LIST OF SUPPLEMENTARY FIGURES
Suppl. Figure 1: Generation of recombinant GST-tagged JAB1 (Immobilized-GST fusion protein) 73
Suppl. Figure 2: Generation of recombinant 6XHis-tagged pre-S peptides used in this study. 74
Suppl. Figure 3: N-terminus a.a residue 61-119 of 2-LHBs is necessary for the interaction of ∆2-LHBs and JAB1. 75
Suppl. Figure 4: Purification of 6X His-tagged pre-S variants 76
Suppl. Figure 5: Generation of purified GST protein 77




LIST OF APPENDICES
Appendix 1: HBV serotypes 78
Appendix 2: HBV virion and genome structure 79
Appendix 3: The replication cycle of Hepatitis B virus 80
Appendix 4: pre-S variants and GGH morphology 81
Appendix 5: Schematic depiction of the potential signals induced by pre-S mutants and in ground glass hepatocyte (GGH). 82
Appendix 6: Model of pre-S2 mutant LHBs-related HCC 83
Appendix 7: MSI analysis system locus information. 84
Appendix 8: Example of MSI analysis system by Genescan 85
Appendix 9: Association of JAB1 with 2-LHBs is through N-terminal amino acid residues 61-119 of 2-LHBs. 86
Appendix 10: Schematic of in vitro GST pull-down assay using bacterial expression of bait and prey proteins. 87
Appendix 11: pET-21 and PGEX-5X-1 vector maps. 88

參考文獻 REFERENCES
Abdo, A.A., B.M. Al-Jarallah, F.M. Sanai, A.S. Hersi, K. Al-Swat, N.A. Azzam, M. Al-Dukhayil, A. Al-Maarik, and F.Z. Al-Faleh. 2006. Hepatitis B genotypes: relation to clinical outcome in patients with chronic hepatitis B in Saudi Arabia. World J Gastroenterol. 12:7019-7024.
Aguilera, A., and B. Gomez-Gonzalez. 2008. Genome instability: a mechanistic view of its causes and consequences. Nat Rev Genet. 9:204-217.
Alvarado-Esquivel, C., E. Sablon, C.J. Conde-Gonzalez, L. Juarez-Figueroa, L. Ruiz-Maya, and S. Aguilar-Benavides. 2006. Molecular analysis of hepatitis B virus isolates in Mexico: predominant circulation of hepatitis B virus genotype H. World J Gastroenterol. 12:6540-6545.
Andernach, I.E., C. Nolte, J.W. Pape, and C.P. Muller. 2009. Slave trade and hepatitis B virus genotypes and subgenotypes in Haiti and Africa. Emerg Infect Dis. 15:1222-1228.
Bacher, J.W., L.A. Flanagan, R.L. Smalley, N.A. Nassif, L.J. Burgart, R.B. Halberg, W.M. Megid, and S.N. Thibodeau. 2004. Development of a fluorescent multiplex assay for detection of MSI-High tumors. Dis Markers. 20:237-250.
Bock, C.T., H.L. Tillmann, M.P. Manns, and C. Trautwein. 1999. The pre-S region determines the intracellular localization and appearance of hepatitis B virus. Hepatology. 30:517-525.
Boland, C.R., S.N. Thibodeau, S.R. Hamilton, D. Sidransky, J.R. Eshleman, R.W. Burt, S.J. Meltzer, M.A. Rodriguez-Bigas, R. Fodde, G.N. Ranzani, and S. Srivastava. 1998. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 58:5248-5257.
Bouchard, M.J., and R.J. Schneider. 2004. The enigmatic X gene of hepatitis B virus. J Virol. 78:12725-12734.
Bozdayi, G., A.R. Turkyilmaz, R. Idilman, E. Karatayli, S. Rota, C. Yurdaydin, and A.M. Bozdayi. 2005. Complete genome sequence and phylogenetic analysis of hepatitis B virus isolated from Turkish patients with chronic HBV infection. J Med Virol. 76:476-481.
Brechot, C., V. Thiers, D. Kremsdorf, B. Nalpas, S. Pol, and P. Paterlini-Brechot. 2001. Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely "occult"? Hepatology. 34:194-203.
Bronner, C.E., S.M. Baker, P.T. Morrison, G. Warren, L.G. Smith, M.K. Lescoe, M. Kane, C. Earabino, J. Lipford, A. Lindblom, and et al. 1994. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature. 368:258-261.
Bruix, J., and M. Sherman. 2005. Management of hepatocellular carcinoma. Hepatology. 42:1208-1236.
Buendia, M.A. 2000. Genetics of hepatocellular carcinoma. Semin Cancer Biol. 10:185-200.
Burk, R.D., L.Y. Hwang, G.Y. Ho, D.A. Shafritz, and R.P. Beasley. 1994. Outcome of perinatal hepatitis B virus exposure is dependent on maternal virus load. J Infect Dis. 170:1418-1423.
Cavinta, L., G. Cao, and S. Schaefer. 2009a. Description of a new hepatitis B virus C6 subgenotype found in the Papua province of Indonesia and suggested renaming of a tentative C6 subgenotype found in the Philippines as subgenotype C7. J Clin Microbiol. 47:3068-3069.
Cavinta, L., J. Sun, A. May, J. Yin, M. von Meltzer, M. Radtke, N.G. Barzaga, G. Cao, and S. Schaefer. 2009b. A new isolate of hepatitis B virus from the Philippines possibly representing a new subgenotype C6. J Med Virol. 81:983-987.
Chan, H.L., and J.J. Sung. 2006. Hepatocellular carcinoma and hepatitis B virus. Semin Liver Dis. 26:153-161.
Chandra, P.K., A. Biswas, S. Datta, A. Banerjee, R. Panigrahi, S. Chakrabarti, B.K. De, and R. Chakravarty. 2009. Subgenotypes of hepatitis B virus genotype D (D1, D2, D3 and D5) in India: differential pattern of mutations, liver injury and occult HBV infection. J Viral Hepat. 16:749-756.
Chang, M.H., S.L. You, C.J. Chen, C.J. Liu, C.M. Lee, S.M. Lin, H.C. Chu, T.C. Wu, S.S. Yang, H.S. Kuo, and D.S. Chen. 2009. Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study. J Natl Cancer Inst. 101:1348-1355.
Chang, S.F., H.J. Netter, M. Bruns, R. Schneider, K. Frolich, and H. Will. 1999. A new avian hepadnavirus infecting snow geese (Anser caerulescens) produces a significant fraction of virions containing single-stranded DNA. Virology. 262:39-54.
Chen, B.F., C.J. Liu, G.M. Jow, P.J. Chen, J.H. Kao, and D.S. Chen. 2006a. High prevalence and mapping of pre-S deletion in hepatitis B virus carriers with progressive liver diseases. Gastroenterology. 130:1153-1168.
Chen, C.J., U.H. Iloeje, and H.I. Yang. 2007a. Long-term outcomes in hepatitis B: the REVEAL-HBV study. Clin Liver Dis. 11:797-816, viii.
Chen, G., W. Lin, F. Shen, U.H. Iloeje, W.T. London, and A.A. Evans. 2006b. Past HBV viral load as predictor of mortality and morbidity from HCC and chronic liver disease in a prospective study. Am J Gastroenterol. 101:1797-1803.
Chen, J., J. Yin, X. Tan, H. Zhang, B. Chen, W. Chang, S. Schaefer, and G. Cao. 2007b. Improved multiplex-PCR to identify hepatitis B virus genotypes A-F and subgenotypes B1, B2, C1 and C2. J Clin Virol. 38:238-243.
Cross, J.C., P. Wen, and W.J. Rutter. 1993. Transactivation by hepatitis B virus X protein is promiscuous and dependent on mitogen-activated cellular serine/threonine kinases. Proc Natl Acad Sci U S A. 90:8078-8082.
de la Chapelle, A. 1999. Testing tumors for microsatellite instability. Eur J Hum Genet. 7:407-408.
Dejean, A., L. Bougueleret, K.H. Grzeschik, and P. Tiollais. 1986. Hepatitis B virus DNA integration in a sequence homologous to v-erb-A and steroid receptor genes in a hepatocellular carcinoma. Nature. 322:70-72.
Demokan, S., Y. Suoglu, D. Demir, M. Gozeler, and N. Dalay. 2006. Microsatellite instability and methylation of the DNA mismatch repair genes in head and neck cancer. Ann Oncol. 17:995-999.
Deterding, K., I. Constantinescu, F.D. Nedelcu, J. Gervain, V. Nemecek, O. Srtunecky, A. Vince, I. Grgurevic, K.P. Bielawski, M. Zalewska, T. Bock, A. Ambrozaitis, J. Stanczak, M. Takacs, V. Chulanov, J. Slusarczyk, M. Drazd'akova, J. Wiegand, M. Cornberg, M.P. Manns, and H. Wedemeyer. 2008. Prevalence of HBV genotypes in Central and Eastern Europe. J Med Virol. 80:1707-1711.
Di Lello, F.A., Y.L.F.G. Pineiro, G. Munoz, and R.H. Campos. 2009. Diversity of hepatitis B and C viruses in Chile. J Med Virol. 81:1887-1894.
Dietmaier, W., S. Wallinger, T. Bocker, F. Kullmann, R. Fishel, and J. Ruschoff. 1997. Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression. Cancer Res. 57:4749-4756.
El-Serag, H.B., and K.L. Rudolph. 2007. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 132:2557-2576.
Fan, Y.F., C.C. Lu, Y.C. Chang, T.T. Chang, P.W. Lin, H.Y. Lei, and I.J. Su. 2000. Identification of a pre-S2 mutant in hepatocytes expressing a novel marginal pattern of surface antigen in advanced diseases of chronic hepatitis B virus infection. J Gastroenterol Hepatol. 15:519-528.
Fan, Y.F., C.C. Lu, W.C. Chen, W.J. Yao, H.C. Wang, T.T. Chang, H.Y. Lei, A.L. Shiau, and I.J. Su. 2001. Prevalence and significance of hepatitis B virus (HBV) pre-S mutants in serum and liver at different replicative stages of chronic HBV infection. Hepatology. 33:277-286.
Feitelson, M.A., B. Sun, N.L. Satiroglu Tufan, J. Liu, J. Pan, and Z. Lian. 2002. Genetic mechanisms of hepatocarcinogenesis. Oncogene. 21:2593-2604.
Fishel, R., M.K. Lescoe, M.R. Rao, N.G. Copeland, N.A. Jenkins, J. Garber, M. Kane, and R. Kolodner. 1993. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 75:1027-1038.
Ganem, D. 1991. Assembly of hepadnaviral virions and subviral particles. Curr Top Microbiol Immunol. 168:61-83.
Ganem, D., and R.J. Schneider. 2001. Hepadnaviridae: the viruses and their replication. In Fields virology. Vol. 2. D.M. Knipe and P.M. Howley, editors. Lippincott Williams & Wilkins, Philadelphia. 2923-2969.
Ganem, D., and H.E. Varmus. 1987. The molecular biology of the hepatitis B viruses. Annu Rev Biochem. 56:651-693.
Gavilanes, F., J.M. Gonzalez-Ros, and D.L. Peterson. 1982. Structure of hepatitis B surface antigen. Characterization of the lipid components and their association with the viral proteins. J Biol Chem. 257:7770-7777.
Gerlich, W.H., R. Deepen, K.H. Heermann, B. Krone, X.Y. Lu, M. Seifer, and R. Thomssen. 1990. Protective potential of hepatitis B virus antigens other than the S gene protein. Vaccine. 8 Suppl:S63-68; discussion S79-80.
Goldstein, D.B., A. Ruiz Linares, L.L. Cavalli-Sforza, and M.W. Feldman. 1995. An evaluation of genetic distances for use with microsatellite loci. Genetics. 139:463-471.
Goldstein, S.T., F. Zhou, S.C. Hadler, B.P. Bell, E.E. Mast, and H.S. Margolis. 2005. A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol. 34:1329-1339.
Gomaa, A.I., S.A. Khan, M.B. Toledano, I. Waked, and S.D. Taylor-Robinson. 2008. Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. World J Gastroenterol. 14:4300-4308.
Govindarajan, S., J.R. Craig, and B. Valinluck. 1988. Clonal origin of hepatitis B virus-associated hepatocellular carcinoma. Hum Pathol. 19:403-405.
Hadziyannis, S., M.A. Gerber, C. Vissoulis, and H. Popper. 1973. Cytoplasmic hepatitis B antigen in "ground-glass" hepatocytes of carriers. Arch Pathol. 96:327-330.
Hadziyannis, S.J., and G.V. Papatheodoridis. 2006. Hepatitis B e antigen-negative chronic hepatitis B: natural history and treatment. Semin Liver Dis. 26:130-141.
Hatton, T., S. Zhou, and D.N. Standring. 1992. RNA- and DNA-binding activities in hepatitis B virus capsid protein: a model for their roles in viral replication. J Virol. 66:5232-5241.
Herath, N.I., B.A. Leggett, and G.A. MacDonald. 2006. Review of genetic and epigenetic alterations in hepatocarcinogenesis. J Gastroenterol Hepatol. 21:15-21.
Hoang, J.M., P.H. Cottu, B. Thuille, R.J. Salmon, G. Thomas, and R. Hamelin. 1997. BAT-26, an indicator of the replication error phenotype in colorectal cancers and cell lines. Cancer Res. 57:300-303.
Hollinger, F.B., and D.T. Lau. 2006. Hepatitis B: the pathway to recovery through treatment. Gastroenterol Clin North Am. 35:425-461, x.
Hollinger, F.B., and T.J. Liang. 2001. Hepatitis B virus. In Fields Virology. Vol. 2. D.M. Knipe and P.M. Howley, editors. Lippincott Williams and Wilkins, Philadelphia. 2971–3036.
Horii, A., H.J. Han, M. Shimada, A. Yanagisawa, Y. Kato, H. Ohta, W. Yasui, E. Tahara, and Y. Nakamura. 1994. Frequent replication errors at microsatellite loci in tumors of patients with multiple primary cancers. Cancer Res. 54:3373-3375.
Hsia, C.C., H. Yuwen, and E. Tabor. 1996. Hot-spot mutations in hepatitis B virus X gene in hepatocellular carcinoma. Lancet. 348:625-626.
Hsieh, Y.H., I.J. Su, H.C. Wang, W.W. Chang, H.Y. Lei, M.D. Lai, W.T. Chang, and W. Huang. 2004. Pre-S mutant surface antigens in chronic hepatitis B virus infection induce oxidative stress and DNA damage. Carcinogenesis. 25:2023-2032.
Hsieh, Y.H., I.J. Su, H.C. Wang, J.H. Tsai, Y.J. Huang, W.W. Chang, M.D. Lai, H.Y. Lei, and W. Huang. 2007. Hepatitis B virus pre-S2 mutant surface antigen induces degradation of cyclin-dependent kinase inhibitor p27Kip1 through c-Jun activation domain-binding protein 1. Mol Cancer Res. 5:1063-1072.
Hsu, H.C., T.T. Wu, M.Z. Wu, C.Y. Wu, T.J. Chiou, J.C. Sheu, C.S. Lee, and D.S. Chen. 1988. Evolution of expression of hepatitis B surface and core antigens (HBsAg, HBcAg) in resected primary and recurrent hepatocellular carcinoma in HBsAg carriers in Taiwan. Correlation with local host immune response. Cancer. 62:915-921.
Hu, Z., Z. Zhang, J.W. Kim, Y. Huang, and T.J. Liang. 2006. Altered proteolysis and global gene expression in hepatitis B virus X transgenic mouse liver. J Virol. 80:1405-1413.
Hubschen, J.M., I.E. Andernach, and C.P. Muller. 2008. Hepatitis B virus genotype E variability in Africa. J Clin Virol. 43:376-380.
Huy, T.T., H. Ushijima, K.M. Win, P. Luengrojanakul, P.K. Shrestha, Z.H. Zhong, A.V. Smirnov, T.C. Taltavull, T. Sata, and K. Abe. 2003. High prevalence of hepatitis B virus pre-s mutant in countries where it is endemic and its relationship with genotype and chronicity. J Clin Microbiol. 41:5449-5455.
Iloeje, U.H., H.I. Yang, J. Su, C.L. Jen, S.L. You, and C.J. Chen. 2006. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 130:678-686.
Jarne, P., and P.J.L. Lagoda. 1996. Microsatellites, from molecules to populations and back. Trends in Ecology & Evolution. 11:424-429.
Jemal, A., R. Siegel, J. Xu, and E. Ward. 2010. Cancer statistics, 2010. CA Cancer J Clin. 60:277-300.
Josep, M.L., B. Andrew, and B. Jordi. 2003. Hepatocellular carcinoma. The Lancet. 362:1907-1917.
Kann, M., A. Schmitz, and B. Rabe. 2007. Intracellular transport of hepatitis B virus. World J Gastroenterol. 13:39-47.
Kao, J.H., and D.S. Chen. 2002. Global control of hepatitis B virus infection. Lancet Infect Dis. 2:395-403.
Kao, J.H., P.J. Chen, M.Y. Lai, and D.S. Chen. 2000. Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology. 118:554-559.
Karachristos, A., T. Liloglou, J.K. Field, E. Deligiorgi, E. Kouskouni, and D.A. Spandidos. 1999. Microsatellite instability and p53 mutations in hepatocellular carcinoma. Mol Cell Biol Res Commun. 2:155-161.
Kay, A., and F. Zoulim. 2007. Hepatitis B virus genetic variability and evolution. Virus Res. 127:164-176.
Kensler, T.W., P.A. Egner, J.B. Wang, Y.R. Zhu, B.C. Zhang, P.X. Lu, J.G. Chen, G.S. Qian, S.Y. Kuang, P.E. Jackson, S.J. Gange, L.P. Jacobson, A. Munoz, and J.D. Groopman. 2004. Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas. Gastroenterology. 127:S310-318.
Kim, C.M., K. Koike, I. Saito, T. Miyamura, and G. Jay. 1991. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature. 351:317-320.
Kirschberg, O., C. Schuttler, R. Repp, and S. Schaefer. 2004. A multiplex-PCR to identify hepatitis B virus--enotypes A-F. J Clin Virol. 29:39-43.
Kock, J., and H.J. Schlicht. 1993. Analysis of the earliest steps of hepadnavirus replication: genome repair after infectious entry into hepatocytes does not depend on viral polymerase activity. J Virol. 67:4867-4874.
Kramvis, A., and M.C. Kew. 2007. Epidemiology of hepatitis B virus in Africa, its genotypes and clinical associations of genotypes. Hepatol Res. 37:S9-S19.
Kuang, S.Y., P.E. Jackson, J.B. Wang, P.X. Lu, A. Munoz, G.S. Qian, T.W. Kensler, and J.D. Groopman. 2004. Specific mutations of hepatitis B virus in plasma predict liver cancer development. Proc Natl Acad Sci U S A. 101:3575-3580.
Lai, C.L., V. Ratziu, M.F. Yuen, and T. Poynard. 2003. Viral hepatitis B. Lancet. 362:2089-2094.
Lavanchy, D. 2005. Worldwide epidemiology of HBV infection, disease burden, and vaccine prevention. J Clin Virol. 34 Suppl 1:S1-3.
Legendre, M., N. Pochet, T. Pak, and K.J. Verstrepen. 2007. Sequence-based estimation of minisatellite and microsatellite repeat variability. Genome Res. 17:1787-1796.
Levrero, M., T. Pollicino, J. Petersen, L. Belloni, G. Raimondo, and M. Dandri. 2009. Control of cccDNA function in hepatitis B virus infection. J Hepatol. 51:581-592.
Li, S.P., H.Y. Wang, J.Q. Li, C.Q. Zhang, Q.S. Feng, P. Huang, X.J. Yu, L.X. Huang, Q.W. Liang, and Y.X. Zeng. 2001. Genome-wide analyses on loss of heterozygosity in hepatocellular carcinoma in Southern China. J Hepatol. 34:840-849.
Li, Y.C., A.B. Korol, T. Fahima, A. Beiles, and E. Nevo. 2002. Microsatellites: genomic distribution, putative functions and mutational mechanisms: a review. Mol Ecol. 11:2453-2465.
Lin, C.L., C.H. Liu, W. Chen, W.L. Huang, P.J. Chen, M.Y. Lai, D.S. Chen, and J.H. Kao. 2007. Association of pre-S deletion mutant of hepatitis B virus with risk of hepatocellular carcinoma. J Gastroenterol Hepatol. 22:1098-1103.
Liu, C.J., and J.H. Kao. 2007. Hepatitis B virus-related hepatocellular carcinoma: epidemiology and pathogenic role of viral factors. J Chin Med Assoc. 70:141-145.
Livingston, S.E., J.P. Simonetti, B.J. McMahon, L.R. Bulkow, K.J. Hurlburt, C.E. Homan, M.M. Snowball, H.H. Cagle, J.L. Williams, and V.P. Chulanov. 2007. Hepatitis B virus genotypes in Alaska Native people with hepatocellular carcinoma: preponderance of genotype F. J Infect Dis. 195:5-11.
Lu, C.C., M. Chen, J.H. Ou, and T.S. Yen. 1995. Key role of a CCAAT element in regulating hepatitis B virus surface protein expression. Virology. 206:1155-1158.
Ma, W.L., C.L. Hsu, M.H. Wu, C.T. Wu, C.C. Wu, J.J. Lai, Y.S. Jou, C.W. Chen, S. Yeh, and C. Chang. 2008. Androgen receptor is a new potential therapeutic target for the treatment of hepatocellular carcinoma. Gastroenterology. 135:947-955, 955 e941-945.
Maddrey, W.C. 2000. Hepatitis B: an important public health issue. J Med Virol. 61:362-366.
Marion, P.L., L.S. Oshiro, D.C. Regnery, G.H. Scullard, and W.S. Robinson. 1980. A virus in Beechey ground squirrels that is related to hepatitis B virus of humans. Proc Natl Acad Sci U S A. 77:2941-2945.
Masaadeh, H.A., W.A. Hayajneh, and E.A. Alqudah. 2008. Hepatitis B virus genotypes and lamivudine resistance mutations in Jordan. World J Gastroenterol. 14:7231-7234.
Mason, W.S., G. Seal, and J. Summers. 1980. Virus of Pekin ducks with structural and biological relatedness to human hepatitis B virus. J Virol. 36:829-836.
Mauss, S., T. Berg, J. Rockstroh, C. Sarrazin, and H. Wedemeyer. 2010. Hepatology - A Clinical Textbook. Flying Publisher.
McMahon, B.J. 2004. The natural history of chronic hepatitis B virus infection. Semin Liver Dis. 24 Suppl 1:17-21.
Meldal, B.H., N.M. Moula, I.H. Barnes, K. Boukef, and J.P. Allain. 2009. A novel hepatitis B virus subgenotype, D7, in Tunisian blood donors. J Gen Virol. 90:1622-1628.
Metzgar, D., L. Liu, C. Hansen, K. Dybvig, and C. Wills. 2002. Domain-level differences in microsatellite distribution and content result from different relative rates of insertion and deletion mutations. Genome Res. 12:408-413.
Michielsen, P.P., S.M. Francque, and J.L. van Dongen. 2005. Viral hepatitis and hepatocellular carcinoma. World J Surg Oncol. 3:27.
Milich, D.R., J.E. Jones, A. McLachlan, G. Bitter, A. Moriarty, and J.L. Hughes. 1990. Importance of subtype in the immune response to the pre-S(2) region of the hepatitis B surface antigen. II. Synthetic Pre-S(2) immunogen. J Immunol. 144:3544-3551.
Mojiri, A., A. Behzad-Behbahani, M. Saberifirozi, M. Ardabili, M. Beheshti, M. Rahsaz, M. Banihashemi, N. Azarpira, B. Geramizadeh, B. Khadang, A. Moaddeb, M. Ghaedi, T. Heidari, A. Torab, A. Salah, S. Amirzadeh, Z. Jowkar, D. Mehrabani, S. Amini-Bavil-Olyaee, and M.A. Dehyadegari. 2008. Hepatitis B virus genotypes in southwest Iran: molecular, serological and clinical outcomes. World J Gastroenterol. 14:1510-1513.
Moriya, K., H. Fujie, Y. Shintani, H. Yotsuyanagi, T. Tsutsumi, K. Ishibashi, Y. Matsuura, S. Kimura, T. Miyamura, and K. Koike. 1998. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med. 4:1065-1067.
Mulyanto, S.N. Depamede, K. Surayah, F. Tsuda, K. Ichiyama, M. Takahashi, and H. Okamoto. 2009. A nationwide molecular epidemiological study on hepatitis B virus in Indonesia: identification of two novel subgenotypes, B8 and C7. Arch Virol. 154:1047-1059.
Murakami, S. 1999. Hepatitis B virus X protein: structure, function and biology. Intervirology. 42:81-99.
Murakami, S. 2001. Hepatitis B virus X protein: a multifunctional viral regulator. Journal of Gastroenterology. 36:651-660.
Murakami, S., J.H. Cheong, S. Kaneko, and e. al. 1994. Autoregulation of human hepatitis B virus X gene. In Viral Hepatitis and Liver Diseases. Vol. Tokyo: Springer Verlag. K. Nishioka, Suzuki, H, Mishiro, S, Oda, T, (Eds.), editor. 743-747.
Murakami, Y., K. Saigo, H. Takashima, M. Minami, T. Okanoue, C. Brechot, and P. Paterlini-Brechot. 2005. Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas. Gut. 54:1162-1168.
Nakamoto, Y., L.G. Guidotti, C.V. Kuhlen, P. Fowler, and F.V. Chisari. 1998. Immune pathogenesis of hepatocellular carcinoma. J Exp Med. 188:341-350.
Nassal, M. 2008. Hepatitis B viruses: reverse transcription a different way. Virus Res. 134:235-249.
Neurath, A.R., B. Seto, and N. Strick. 1989. Antibodies to synthetic peptides from the preS1 region of the hepatitis B virus (HBV) envelope (env) protein are virus-neutralizing and protective. Vaccine. 7:234-236.
Nijhara, R., S.S. Jana, S.K. Goswami, V. Kumar, and D.P. Sarkar. 2001a. An internal segment (residues 58-119) of the hepatitis B virus X protein is sufficient to activate MAP kinase pathways in mouse liver. FEBS Lett. 504:59-64.
Nijhara, R., S.S. Jana, S.K. Goswami, A. Rana, S.S. Majumdar, V. Kumar, and D.P. Sarkar. 2001b. Sustained activation of mitogen-activated protein kinases and activator protein 1 by the hepatitis B virus X protein in mouse hepatocytes in vivo. J Virol. 75:10348-10358.
Norder, H., A.M. Courouce, P. Coursaget, J.M. Echevarria, S.D. Lee, I.K. Mushahwar, B.H. Robertson, S. Locarnini, and L.O. Magnius. 2004. Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology. 47:289-309.
Norder, H., A.M. Courouce, and L.O. Magnius. 1992a. Molecular basis of hepatitis B virus serotype variations within the four major subtypes. J Gen Virol. 73 ( Pt 12):3141-3145.
Norder, H., B. Hammas, S. Lofdahl, A.M. Courouce, and L.O. Magnius. 1992b. Comparison of the amino acid sequences of nine different serotypes of hepatitis B surface antigen and genomic classification of the corresponding hepatitis B virus strains. J Gen Virol. 73 ( Pt 5):1201-1208.
Nurainy, N., D.H. Muljono, H. Sudoyo, and S. Marzuki. 2008. Genetic study of hepatitis B virus in Indonesia reveals a new subgenotype of genotype B in east Nusa Tenggara. Arch Virol. 153:1057-1065.
Okamoto, H., M. Imai, F. Tsuda, T. Tanaka, Y. Miyakawa, and M. Mayumi. 1987. Point mutation in the S gene of hepatitis B virus for a d/y or w/r subtypic change in two blood donors carrying a surface antigen of compound subtype adyr or adwr. J Virol. 61:3030-3034.
Olinger, C.M., P. Jutavijittum, J.M. Hubschen, A. Yousukh, B. Samountry, T. Thammavong, K. Toriyama, and C.P. Muller. 2008. Possible new hepatitis B virus genotype, southeast Asia. Emerg Infect Dis. 14:1777-1780.
Olinger, C.M., V. Venard, M. Njayou, A.O. Oyefolu, I. Maiga, A.J. Kemp, S.A. Omilabu, A. le Faou, and C.P. Muller. 2006. Phylogenetic analysis of the precore/core gene of hepatitis B virus genotypes E and A in West Africa: new subtypes, mixed infections and recombinations. J Gen Virol. 87:1163-1173.
Osiowy, C., D. Gordon, J. Borlang, E. Giles, and J.P. Villeneuve. 2008. Hepatitis B virus genotype G epidemiology and co-infection with genotype A in Canada. J Gen Virol. 89:3009-3015.
Parkin, D.M., F. Bray, J. Ferlay, and P. Pisani. 2005. Global cancer statistics, 2002. CA Cancer J Clin. 55:74-108.
Perucho, M. 1999. Correspondence re: C.R. Boland et al., A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res., 58: 5248-5257, 1998. Cancer Res. 59:249-256.
Piao, Z., H. Kim, S. Malkhosyan, and C. Park. 2000. Frequent chromosomal instability but no microsatellite instability in hepatocellular carcinomas. Int J Oncol. 17:507-512.
Popper, H. 1975. The ground glass hepatocyte as a diagnostic hint. Hum Pathol. 6:517-520.
Prassolov, A., H. Hohenberg, T. Kalinina, C. Schneider, L. Cova, O. Krone, K. Frolich, H. Will, and H. Sirma. 2003. New hepatitis B virus of cranes that has an unexpected broad host range. J Virol. 77:1964-1976.
Pult, I., H.J. Netter, M. Bruns, A. Prassolov, H. Sirma, H. Hohenberg, S.F. Chang, K. Frolich, O. Krone, E.F. Kaleta, and H. Will. 2001. Identification and analysis of a new hepadnavirus in white storks. Virology. 289:114-128.
Queller, D.C., J.E. Strassmann, and C.R. Hughes. 1993. Microsatellites and kinship. Trends in Ecology & Evolution. 8:285-288.
Rantala, M., and M.J. van de Laar. 2008. Surveillance and epidemiology of hepatitis B and C in Europe - a review. Euro Surveill. 13.
Robinson, W.S. 1994. Molecular events in the pathogenesis of hepadnavirus-associated hepatocellular carcinoma. Annu Rev Med. 45:297-323.
Rockman, M.V., and G.A. Wray. 2002. Abundant raw material for cis-regulatory evolution in humans. Mol Biol Evol. 19:1991-2004.
Sakamoto, T., Y. Tanaka, E. Orito, J. Co, J. Clavio, F. Sugauchi, K. Ito, A. Ozasa, A. Quino, R. Ueda, J. Sollano, and M. Mizokami. 2006. Novel subtypes (subgenotypes) of hepatitis B virus genotypes B and C among chronic liver disease patients in the Philippines. J Gen Virol. 87:1873-1882.
Salvucci, M., A. Lemoine, R. Saffroy, D. Azoulay, B. Lepere, S. Gaillard, H. Bismuth, M. Reynes, and B. Debuire. 1999. Microsatellite instability in European hepatocellular carcinoma. Oncogene. 18:181-187.
Samowitz, W.S., and M.L. Slattery. 1999. Regional reproducibility of microsatellite instability in sporadic colorectal cancer. Genes Chromosomes Cancer. 26:106-114.
Sasiadek, M., A. Stembalska-Kozlowska, R. Smigiel, T. Krecicki, N. Blin, and F. Mirghomizadeh. 2001. Microsatellite and chromosome instability in squamous cell laryngeal carcinoma. Int J Oncol. 19:401-405.
Schaefer, S. 2005. Hepatitis B virus: significance of genotypes. J Viral Hepat. 12:111-124.
Schaefer, S. 2007a. Hepatitis B virus genotypes in Europe. Hepatol Res. 37:S20-26.
Schaefer, S. 2007b. Hepatitis B virus taxonomy and hepatitis B virus genotypes. World J Gastroenterol. 13:14-21.
Schutte, K., J. Bornschein, and P. Malfertheiner. 2009. Hepatocellular carcinoma--epidemiological trends and risk factors. Dig Dis. 27:80-92.
Seeger, C., and W.S. Mason. 2000. Hepatitis B virus biology. Microbiol Mol Biol Rev. 64:51-68.
Seitz, S., S. Urban, C. Antoni, and B. Bottcher. 2007. Cryo-electron microscopy of hepatitis B virions reveals variability in envelope capsid interactions. Embo J. 26:4160-4167.
Shen, F.C., I.J. Su, H.C. Wu, Y.H. Hsieh, W.J. Yao, K.C. Young, T.C. Chang, H.C. Hsieh, H.N. Tsai, and W. Huang. 2009. A pre-S gene chip to detect pre-S deletions in hepatitis B virus large surface antigen as a predictive marker for hepatoma risk in chronic hepatitis B virus carriers. J Biomed Sci. 16:84.
Sheu, J.C., Y.W. Lin, H.C. Chou, G.T. Huang, H.S. Lee, Y.H. Lin, S.Y. Huang, C.H. Chen, J.T. Wang, P.H. Lee, J.T. Lin, F.J. Lu, and D.S. Chen. 1999. Loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in Taiwan. Br J Cancer. 80:468-476.
Shikata, T. 1973. Australia antigen in liver tissue--an immunofluorescent and immunoelectron microscopic study. Jpn J Exp Med. 43:231-245.
Shikata, T., T. Uzawa, N. Yoshiwara, T. Akatsuka, and S. Yamazaki. 1974. Staining methods of Australia antigen in paraffin section--detection of cytoplasmic inclusion bodies. Jpn J Exp Med. 44:25-36.
Smigiel, R., A. Stembalska-Kozlowska, F. Mirghomizadeh, T. Krecicki, T. Zatonski, D. Ramsey, M. Horobiowska, J. Jagielski, N. Blin, and M. Sasiadek. 2004. Correlation among loss of heterozygosity, promoter methylation and protein expression of MLH1 in larynx cancer. Oncol Rep. 11:707-710.
Sprengel, R., E.F. Kaleta, and H. Will. 1988. Isolation and characterization of a hepatitis B virus endemic in herons. J Virol. 62:3832-3839.
Starkman, S.E., D.M. MacDonald, J.C. Lewis, E.C. Holmes, and P. Simmonds. 2003. Geographic and species association of hepatitis B virus genotypes in non-human primates. Virology. 314:381-393.
Su, I.J., H.C. Wang, H.C. Wu, and W.Y. Huang. 2008. Ground glass hepatocytes contain pre-S mutants and represent preneoplastic lesions in chronic hepatitis B virus infection. J Gastroenterol Hepatol. 23:1169-1174.
Summers, J., J.M. Smolec, and R. Snyder. 1978. A virus similar to human hepatitis B virus associated with hepatitis and hepatoma in woodchucks. Proc Natl Acad Sci U S A. 75:4533-4537.
Suraweera, N., A. Duval, M. Reperant, C. Vaury, D. Furlan, K. Leroy, R. Seruca, B. Iacopetta, and R. Hamelin. 2002. Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology. 123:1804-1811.
Tai, P.C., D. Banik, G.I. Lin, S. Pai, K. Pai, M.H. Lin, G. Yuoh, S. Che, S.H. Hsu, T.C. Chen, T.T. Kuo, C.S. Lee, C.S. Yang, and C. Shih. 1997. Novel and frequent mutations of hepatitis B virus coincide with a major histocompatibility complex class I-restricted T-cell epitope of the surface antigen. J Virol. 71:4852-4856.
Tallo, T., V. Tefanova, L. Priimagi, J. Schmidt, O. Katargina, M. Michailov, S. Mukomolov, L. Magnius, and H. Norder. 2008. D2: major subgenotype of hepatitis B virus in Russia and the Baltic region. J Gen Virol. 89:1829-1839.
Tarn, C., S. Lee, Y. Hu, C. Ashendel, and O.M. Andrisani. 2001. Hepatitis B virus X protein differentially activates RAS-RAF-MAPK and JNK pathways in X-transforming versus non-transforming AML12 hepatocytes. J Biol Chem. 276:34671-34680.
Tatematsu, K., Y. Tanaka, F. Kurbanov, F. Sugauchi, S. Mano, T. Maeshiro, T. Nakayoshi, M. Wakuta, Y. Miyakawa, and M. Mizokami. 2009. A genetic variant of hepatitis B virus divergent from known human and ape genotypes isolated from a Japanese patient and provisionally assigned to new genotype J. J Virol. 83:10538-10547.
Tennant, B.C., N. Mrosovsky, K. McLean, P.J. Cote, B.E. Korba, R.E. Engle, J.L. Gerin, J. Wright, G.R. Michener, E. Uhl, and et al. 1991. Hepatocellular carcinoma in Richardson's ground squirrels (Spermophilus richardsonii): evidence for association with hepatitis B-like virus infection. Hepatology. 13:1215-1221.
Testut, P., C.A. Renard, O. Terradillos, L. Vitvitski-Trepo, F. Tekaia, C. Degott, J. Blake, B. Boyer, and M.A. Buendia. 1996. A new hepadnavirus endemic in arctic ground squirrels in Alaska. J Virol. 70:4210-4219.
Thibodeau, S.N., G. Bren, and D. Schaid. 1993. Microsatellite instability in cancer of the proximal colon. Science. 260:816-819.
Thibodeau, S.N., A.J. French, J.M. Cunningham, D. Tester, L.J. Burgart, P.C. Roche, S.K. McDonnell, D.J. Schaid, C.W. Vockley, V.V. Michels, G.H. Farr, Jr., and M.J. O'Connell. 1998. Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1. Cancer Res. 58:1713-1718.
Tiollais, P., C. Pourcel, and A. Dejean. 1985. The hepatitis B virus. Nature. 317:489-495.
Togni, R., N. Bagla, P. Muiesan, R. Miquel, J. O'Grady, N. Heaton, A.S. Knisely, B. Portmann, and A. Quaglia. 2009. Microsatellite instability in hepatocellular carcinoma in non-cirrhotic liver in patients older than 60 years. Hepatol Res. 39:266-273.
Tokino, T., H. Tamura, N. Hori, and K. Matsubara. 1991. Chromosome deletions associated with hepatitis B virus integration. Virology. 185:879-882.
Touraine, R.L., Y. Bertrand, P. Foray, J. Gilly, and N. Philippe. 1993. Hepatic tumours during androgen therapy in Fanconi anaemia. Eur J Pediatr. 152:691-693.
Tran, T.T., T.N. Trinh, and K. Abe. 2008. New complex recombinant genotype of hepatitis B virus identified in Vietnam. J Virol. 82:5657-5663.
Turnpenny, P.D., and S. Ellard. 2005. Emery's elements of medical genetics. Elsevier, London.
Ueda, H., S.J. Ullrich, J.D. Gangemi, C.A. Kappel, L. Ngo, M.A. Feitelson, and G. Jay. 1995. Functional inactivation but not structural mutation of p53 causes liver cancer. Nat Genet. 9:41-47.
Urban, S. 2008. New insights into hepatitis B and hepatitis delta virus entry. In Future Virol. Vol. 3. 253-264.
Urban, S., A. Schulze, M. Dandri, and J. Petersen. 2010. The replication cycle of hepatitis B virus. J Hepatol. 52:282-284.
Utama, A., S. Purwantomo, M.D. Siburian, R. Dhenni, R.A. Gani, I. Hasan, A. Sanityoso, U.A. Miskad, F. Akil, I. Yusuf, W.A. Achwan, S. Soemohardjo, S.A. Lelosutan, R. Martamala, B. Lukito, U. Budihusodo, L.A. Lesmana, A. Sulaiman, and S. Tai. 2009. Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia. World J Gastroenterol. 15:4028-4036.
Utsumi, T., M.I. Lusida, Y. Yano, V.E. Nugrahaputra, M. Amin, Juniastuti, Soetjipto, Y. Hayashi, and H. Hotta. 2009. Complete genome sequence and phylogenetic relatedness of hepatitis B virus isolates in Papua, Indonesia. J Clin Microbiol. 47:1842-1847.
Wang, H.C., W.T. Chang, W.W. Chang, H.C. Wu, W. Huang, H.Y. Lei, M.D. Lai, N. Fausto, and I.J. Su. 2005. Hepatitis B virus pre-S2 mutant upregulates cyclin A expression and induces nodular proliferation of hepatocytes. Hepatology. 41:761-770.
Wang, H.C., H.C. Wu, C.F. Chen, N. Fausto, H.Y. Lei, and I.J. Su. 2003. Different types of ground glass hepatocytes in chronic hepatitis B virus infection contain specific pre-S mutants that may induce endoplasmic reticulum stress. Am J Pathol. 163:2441-2449.
Wang, J., X. Chenivesse, B. Henglein, and C. Brechot. 1990. Hepatitis B virus integration in a cyclin A gene in a hepatocellular carcinoma. Nature. 343:555-557.
Wang, Y., J. Irish, C. MacMillan, D. Brown, Y. Xuan, C. Boyington, P. Gullane, and S. Kamel-Reid. 2001. High frequency of microsatellite instability in young patients with head-and-neck squamous-cell carcinoma: lack of involvement of the mismatch repair genes hMLH1 AND hMSH2. Int J Cancer. 93:353-360.
Wasley, A., S. Grytdal, and K. Gallagher. 2008. Surveillance for acute viral hepatitis--United States, 2006. MMWR Surveill Summ. 57:1-24.
World Health Organization. 2008. Hepatitis B Fact sheet N°204
Xu, Z., G. Jensen, and T.S. Yen. 1997. Activation of hepatitis B virus S promoter by the viral large surface protein via induction of stress in the endoplasmic reticulum. J Virol. 71:7387-7392.
Yamamoto, H., F. Itoh, H. Fukushima, H. Kaneto, S. Sasaki, T. Ohmura, T. Satoh, Y. Karino, T. Endo, J. Toyota, and K. Imai. 2000. Infrequent widespread microsatellite instability in hepatocellular carcinomas. Int J Oncol. 16:543-547.
Yin, J., H. Zhang, C. Li, C. Gao, Y. He, Y. Zhai, P. Zhang, L. Xu, X. Tan, J. Chen, S. Cheng, S. Schaefer, and G. Cao. 2008. Role of hepatitis B virus genotype mixture, subgenotypes C2 and B2 on hepatocellular carcinoma: compared with chronic hepatitis B and asymptomatic carrier state in the same area. Carcinogenesis. 29:1685-1691.
Yu, D.Y., H.B. Moon, J.K. Son, S. Jeong, S.L. Yu, H. Yoon, Y.M. Han, C.S. Lee, J.S. Park, C.H. Lee, B.H. Hyun, S. Murakami, and K.K. Lee. 1999. Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein. J Hepatol. 31:123-132.
Yu, M.W., S.H. Yeh, P.J. Chen, Y.F. Liaw, C.L. Lin, C.J. Liu, W.L. Shih, J.H. Kao, D.S. Chen, and C.J. Chen. 2005. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a prospective study in men. J Natl Cancer Inst. 97:265-272.
Zhang, S.H., W.M. Cong, Z.H. Xian, and M.C. Wu. 2005. Clinicopathological significance of loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in China. World J Gastroenterol. 11:3034-3039.
Zhang, Z., N. Torii, Z. Hu, J. Jacob, and T.J. Liang. 2001. X-deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo. J Clin Invest. 108:1523-1531.

SUPPLEMENTARY REFERENCES
Bimston, D., J. Song, D. Winchester, S. Takayama, J.C. Reed, and R.I. Morimoto. 1998. BAG-1, a negative regulator of Hsp70 chaperone activity, uncouples nucleotide hydrolysis from substrate release. Embo J. 17:6871-6878.
Burger-Kentischer, A., D. Finkelmeier, M. Thiele, J. Schmucker, G. Geiger, G.E. Tovar, and J. Bernhagen. 2005. Binding of JAB1/CSN5 to MIF is mediated by the MPN domain but is independent of the JAMM motif. FEBS Lett. 579:1693-1701.
Hsieh, Y.H., I.J. Su, H.C. Wang, J.H. Tsai, Y.J. Huang, W.W. Chang, M.D. Lai, H.Y. Lei, and W. Huang. 2007. Hepatitis B virus pre-S2 mutant surface antigen induces degradation of cyclin-dependent kinase inhibitor p27Kip1 through c-Jun activation domain-binding protein 1. Mol Cancer Res. 5:1063-1072.
Ito, T., T. Chiba, R. Ozawa, M. Yoshida, M. Hattori, and Y. Sakaki. 2001. A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc Natl Acad Sci U S A. 98:4569-4574.
Sambrook, J., T. Maniatis, and E.F. Fritsch. 1989. Molecular cloning : a laboratory manual / J. Sambrook, E.F. Fritsch, T. Maniatis. New York : Cold Spring Harbor Laboratory Press.
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