Bik-Yu Hui. / "July 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 187-203). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Lo Kwok-Wai. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (p. 171-199). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

by Liu Chun Ki, Kevin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves 126-142). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.ii / Table of contents --- p.iii / List of figures --- p.viii / List of tables --- p.x / List of abbreviations --- p.xi / Chapter Chapter 1 --- Introduction Epstein-Barr Virus / Chapter 1.1 --- History --- p.1 / Chapter 1.2 --- Classification --- p.2 / Chapter 1.3 --- Virus and genome structure --- p.3 / Chapter 1.4 --- Epidemiology --- p.6 / Chapter 1.4.1 --- Prevalence of infection --- p.6 / Chapter 1.4.2 --- Modes of transmission --- p.7 / Chapter 1.5 --- Pathogenesis of EBV --- p.7 / Chapter 1.5.1 --- "Adsorption, penetration and dissemination" --- p.7 / Chapter 1.5.2 --- Lytic infection cycle --- p.8 / Chapter 1.5.3 --- Latent infection cycle --- p.9 / Chapter 1.5.4 --- Functions of the EBV-specific proteins associated with latent infection cycle proteins --- p.10 / Chapter 1.5.4.1 --- EBNA1 --- p.10 / Chapter 1.5.4.2 --- EBNA2 --- p.11 / Chapter 1.5.4.3 --- "EBNA 3A, 3B and 3C" --- p.11 / Chapter 1.5.4.4 --- EBNA LP --- p.12 / Chapter 1.5.4.5 --- LMP1 --- p.13 / Chapter 1.5.4.6 --- Characteristics of EBV LMP 2 gene --- p.14 / Chapter 1.5.4.7 --- Functions of LMP 2A --- p.15 / Chapter 1.5.4.8 --- Functions of LMP 2B --- p.18 / Chapter 1.6 --- Clinical significance of EBV --- p.20 / Chapter 1.6.1 --- Infectious mononucleosis (IM) --- p.20 / Chapter 1.6.2 --- Burkitt's lymphoma (BL) --- p.20 / Chapter 1.6.3 --- Nasopharyngeal carcinoma (NPC) --- p.21 / Chapter 1.6.4 --- Hodgkin's lymphoma (HL) --- p.21 / Chapter 1.7 --- Immune response to EBV infection --- p.22 / Chapter 1.7.1 --- Humoral immune response --- p.22 / Chapter 1.7.2 --- Cellular immune response --- p.22 / Chapter 1.8 --- Diagnosis of EBV infection --- p.26 / Chapter 1.9 --- Treatment and prevention --- p.27 / Chapter 1.10 --- Nasopharygneal Carcinoma (NPC) --- p.28 / Chapter 1.10.1 --- Epidemiology --- p.28 / Chapter 1.10.2 --- Etiology --- p.28 / Chapter 1.10.2.1 --- Environmental factor associated with NPC --- p.30 / Chapter 1.10.2.2 --- Genetic factors associated with NPC --- p.31 / Chapter 1.10.2.3 --- Association of NPC and EBV --- p.31 / Chapter 1.10.3 --- Diagnosis ofNPC --- p.32 / Chapter 1.10.4 --- Treatment --- p.33 / Chapter 1.11 --- Objective of the project --- p.34 / Chapter Chapter 2 --- Materials and Methods / Chapter 2.1 --- EBV-containing cell cultures --- p.35 / Chapter 2.2 --- Extraction of total RNA --- p.36 / Chapter 2.2.1 --- Cell lysis --- p.36 / Chapter 2.2.2 --- Protein digestion --- p.36 / Chapter 2.2.3 --- DNA digestion --- p.37 / Chapter 2.2.4 --- Elution of total RNA --- p.37 / Chapter 2.2.5 --- Purity and electrophoresis analysis of total RNA --- p.38 / Chapter 2.3 --- First strand cDNA synthesis --- p.38 / Chapter 2.4 --- PCR amplification of LMP 2 cDNA --- p.39 / Chapter 2.5 --- Isolation of the PCR amplified LMP 2 cDNA --- p.40 / Chapter 2.6 --- Purification of the PCR amplified LMP 2 cDNA --- p.41 / Chapter 2.7 --- Confirmation of the PCR amplified cDNA --- p.42 / Chapter 2.7.1 --- Nested PCR --- p.42 / Chapter 2.7.2 --- Restriction enzyme digestion --- p.44 / Chapter 2.8 --- Ligation of insert LMP 2 cDNA with vector --- p.45 / Chapter 2.9 --- Transformation of competent cells JM109 --- p.45 / Chapter 2.10 --- Screening of the recombinant clones --- p.47 / Chapter 2.11 --- Small scale purification of plasmid DNA --- p.47 / Chapter 2.12 --- Determination of the size of the insert DNA --- p.48 / Chapter 2.13 --- DNA sequencing --- p.48 / Chapter 2.13.1 --- The cycle sequencing reaction --- p.48 / Chapter 2.13.2 --- Preparation of the acrylamide gel and TBE buffer --- p.51 / Chapter 2.13.3 --- Running conditions of the electrophoresis --- p.52 / Chapter 2.13.4 --- "Processing, editing and exporting the sequences" --- p.52 / Chapter 2.14 --- Data analysis --- p.53 / Chapter 2.14.1 --- Sequence analysis --- p.53 / Chapter 2.14.2 --- Amino acid analysis --- p.53 / Chapter 2.14.3 --- Protein secondary structure analysis --- p.53 / Chapter 2.14.4 --- Hydrophobicity analysis --- p.54 / Chapter 2.14.5 --- Isoelectric point analysis --- p.54 / Chapter Chapter 3 --- Results / Chapter 3.1 --- Cell Cultures --- p.55 / Chapter 3.2 --- Extraction of total RNA --- p.56 / Chapter 3.3 --- PCR amplification --- p.61 / Chapter 3.4 --- Isolation of PCR amplified LMP 2 cDNA --- p.62 / Chapter 3.5 --- Confirmation of the PCR amplified cDNA --- p.66 / Chapter 3.5.1 --- Nested PCR --- p.66 / Chapter 3.5.2 --- Restriction enzyme digestion --- p.71 / Chapter 3.6 --- Transformation and screening --- p.77 / Chapter 3.7 --- Extraction of plasmid DNA and its digestion with restriction enzyme --- p.78 / Chapter 3.8 --- DNA sequencing --- p.83 / Chapter 3.8.1 --- DNA sequence comparison --- p.84 / Chapter 3.9 --- Amino acid sequence homology --- p.89 / Chapter 3.9.1 --- Amino acid sequence comparison --- p.90 / Chapter 3.10 --- Hydrophobicity analysis --- p.92 / Chapter 3.10.1 --- Comparison of hydrophobicity of B95-8 derived LMP2 with GeneBank --- p.93 / Chapter 3.10.2 --- Comparison of hydrophobicity of CB 14022-derived LMP2 with GeneBank --- p.95 / Chapter 3.10.3 --- Comparison of hydrophobicity of Raji-derived LMP2 with GeneBank --- p.97 / Chapter 3.11 --- Protein secondary structure analysis --- p.100 / Chapter 3.11.1 --- Comparison of secondary structure of B95-8-derived LMP2 with GeneBank --- p.100 / Chapter 3.11.2 --- Comparison of secondary structure of CB 14022-derived LMP2 with GeneBank --- p.100 / Chapter 3.11.3 --- Comparison of secondary structure of Raji-derived LMP2 with GeneBank --- p.101 / Chapter 3.12 --- Isoelectric point analysis --- p.103 / Chapter Chapter 4 --- Discussions / Chapter 4.1 --- Overall strategy for the cloning and sequencing of EBV LMP 2 gene --- p.106 / Chapter 4.2 --- Implications of the results obtained in sequencing --- p.107 / Chapter 4.3 --- Results interpretation --- p.108 / Chapter 4.3.1 --- Cell culture --- p.108 / Chapter 4.3.2 --- Extraction of total RNA --- p.108 / Chapter 4.3.3 --- PCR amplification --- p.109 / Chapter 4.3.4 --- Confirmation of the PCR amplified cDNAs using nested PCR --- p.109 / Chapter 4.3.5 --- Confirmation of the PCR amplified cDNAs using restriction enzyme digestion --- p.110 / Chapter 4.3.6 --- Ligation of EBV LMP 2 cDNA to pGEM-T Easy Vector --- p.111 / Chapter 4.3.7 --- Transformation and screening --- p.114 / Chapter 4.3.8 --- Extraction of plasmid DNA and digestion with restriction enzyme --- p.115 / Chapter 4.4 --- DNA sequencing and sequence homology --- p.116 / Chapter 4.5 --- Amino acid sequence homology --- p.117 / Chapter 4.6 --- Hydrophobicity analysis --- p.119 / Chapter 4.7 --- Protein secondary structure analysis --- p.120 / Chapter 4.8 --- Isoelectric point analysis --- p.122 / Chapter 4.9 --- Summary of results --- p.122 / Chapter 4.10 --- Conclusions --- p.124 / References --- p.126

Fan Chung-sze. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references. / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / List of Tables --- p.vii / List of Figures --- p.viii / List of Abbreviations --- p.x / Table of Contents --- p.xi / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Nasopharyngeal Carcinoma --- p.1-1 / Chapter 1.1.1 --- Histology of NPC --- p.1-1 / Chapter 1.1.2 --- Etiological Factors --- p.1-2 / Chapter 1.1.3 --- Genetic Changes in NPC --- p.1-5 / Chapter 1.2 --- Background of Present Study --- p.1-14 / Chapter 1.3 --- Aims of Study --- p.1-15 / Chapter Chapter 2 --- Comparative Genomic Hybridization and Fluorescence In- Situ Hybridization / Chapter 2.1 --- Introduction --- p.2-1 / Chapter 2.2 --- Fluorescence In-Situ Hybridization (FISH) --- p.2-2 / Chapter 2.2.1 --- Principle of FISH --- p.2-2 / Chapter 2.2.2 --- Applications of FISH --- p.2-2 / Chapter 2.2.3 --- Advantages and Limitations --- p.2-5 / Chapter 2.3 --- Comparative Genomic Hybridization (CGH) --- p.2-7 / Chapter 2.3.1 --- Principle of CGH --- p.2-7 / Chapter 2.3.2 --- Applications of CGH --- p.2-8 / Chapter 2.3.3 --- Advantages and Limitations --- p.2-10 / Chapter 2.4 --- Method of CGH --- p.2-13 / Chapter 2.4.1 --- CGH Probe Preparation --- p.2-13 / Chapter 2.4.2 --- CGH Template Preparation --- p.2-21 / Chapter 2.4.3 --- Hybridization --- p.2-23 / Chapter 2.4.4 --- Post-hybridization --- p.2-23 / Chapter 2.4.5 --- Fluorescence Detection --- p.2-24 / Chapter 2.4.6 --- Image Acquisition and Analysis --- p.2-24 / Chapter 2.5 --- Method of Interphase FISH --- p.2-29 / Chapter 2.5.1 --- FISH Probe Preparation --- p.2-29 / Chapter 2.5.2 --- FISH Template Preparation --- p.2-29 / Chapter 2.5.3 --- Hybridization --- p.2-30 / Chapter 2.5.4 --- Post-hybridization --- p.2-30 / Chapter 2.5.5 --- Fluorescence Detection --- p.2-30 / Chapter 2.5.6 --- Scoring of FISH Signals --- p.2-31 / Chapter 2.5.7 --- Threshold Determination --- p.2-31 / Chapter Chapter 3 --- FISH Studies on NPC Biopsies Guided by CGH Information Derived from Cell Lines and Xenografts / Chapter 3.1 --- Introduction --- p.3-1 / Chapter 3.2 --- Materials and Methods --- p.3-3 / Chapter 3.2.1 --- CGH Analysis --- p.3-3 / Chapter 3.2.2 --- Interphase FISH Analysis --- p.3-4 / Chapter 3.2.3 --- Statistical Analysis --- p.3-7 / Chapter 3.3 --- Results / Chapter 3.3.1 --- CGH --- p.3-9 / Chapter 3.3.2 --- Interphase FISH Analysis --- p.3-10 / Chapter 3.3.3 --- Statistical Analysis --- p.3-11 / Chapter 3.4 --- Discussion --- p.3-27 / Chapter 3.4.1 --- CGH --- p.3-27 / Chapter 3.4.2 --- Interphase FISH Analysis --- p.3-31 / Chapter 3.5 --- Summary of This Chapter --- p.3-36 / Chapter Chapter 4 --- CGH Studies on Universally Amplified DNA from Microdissected NPC Biopsies and Interphase FISH Analysis / Chapter 4.1 --- Introduction --- p.4-1 / Chapter 4.2 --- Materials and Methods --- p.4-4 / Chapter 4.2.1 --- CGH on Universally Amplified DNA --- p.4-4 / Chapter 4.2.2 --- Interphase FISH Analysis --- p.4-6 / Chapter 4.2.3 --- Statistical Analysis --- p.4-8 / Chapter 4.3 --- Results --- p.4-9 / Chapter 4.3.1 --- CGH on Universally Amplified DNA --- p.4-9 / Chapter 4.3.2 --- Interphase FISH Analysis --- p.4-10 / Chapter 4.3.3 --- Statistical Analysis --- p.4-11 / Chapter 4.3.4 --- Comparison of CGH and FISH Findings --- p.4-11 / Chapter 4.4 --- Discussions --- p.4-30 / Chapter 4.4.1 --- CGH Findings --- p.4-30 / Chapter 4.4.2 --- Interphase FISH Analysis --- p.4-41 / Chapter 4.4.3 --- Comparison of CGH and FISH Findings --- p.4-43 / Chapter 4.5 --- Summary of This Chapter --- p.4-45 / Chapter Chapter 5 --- Conclusion and Further Studies / Chapter 5.1 --- Conclusion --- p.5-1 / Chapter 5.2 --- Further Studies --- p.5-3 / Chapter 5.2.1 --- Combination of Microdissection --- p.5-3 / Chapter 5.2.2 --- Multicolor Karyotyping --- p.5-3 / Chapter 5.2.3 --- Microarrays --- p.5-4 / References --- p.R-1

by Cheung Siu Tim. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (p. 155-160). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Common amplicons were delineated throughout the NPC genome in a large panel of NPC cell lines, xenografts, and primary tumors by two high-density genomic arrays with ∼1 Mb and 35 kb resolution. Apart from the genetic changes reported in previous studies, a number of novel chromosomal aberrations were discovered, including gains at 7p11, 16p13.3, 19p13, 19q13-q43 and 20q13. Most distinctively, common amplicons at 11q13 and 12p13 were found in this cancer. Two smallest amplification regions with 5.4 Mb and 2.16 Mb were delineated at 11q13.1-q13.3 and 12p13.31 respectively. The high prevalence of these 2 amplified regions have led to the hypothesis that activation of the target oncogenes in these regions are critical events for NPC development. / Expression of candidate genes located within 11q13.3 was examined and consistent overexpression of CCND1 in cell lines and xenografts were identified in the 11q13.3. Frequent concordant gains and overexpression of CCND1 were further confirmed in primary tumors. Knockdown of CCND1 mRNA by siRNA technique was found to inhibit cell growth and lead to cell cycle arrest at G1. Alterations of protein expressions of other cell cycle components were also observed. Moreover, inactivation of p16 and overexpression of cyclin D1 were commonly occurred in NPC. These findings provided evidence that cyclin D1 may have cell cycle-independent functions, which is critical in NPC tumongenesis. / Frequent gains of 12p13.31 region were confirmed by fluorescence in situ hybridization (FISH) analysis. According to expression array and real-time RT-PCR results, LTbetaR, TNFRSF1A and FLJ10665 were the three genes showing concordant amplification and overexpression in NPC xenograft. The LTbetaR protein, which is a lymphotoxin beta receptor, was confirmed to be recurrently overexpressed in NPC primary tumors and its overexpression may be involved in the activation of NF-kappaB in NPC. The findings suggested that it is one of the candidate oncogenes of this cancer. / In summary, three candidate NPC-associated oncogenes locating at 3q26.32, 11q13.3 and 12p13.31 were identified by genome-wide mapping analysis. Molecular and functional characterizations of these genes have provided evidences that they play critical roles in NPC tumorigenesis. / In this study, detailed investigation was carried out on a candidate NPC-associated oncogene, PIK3CA at 38q26.32, an amplicon reported previously. Copy number gains and amplifications of this gene, but not mutation, were demonstrated to be common events in NPC. The findings hence implied the importance of PIK3CA in NPC tumorigenesis. / Nasopharyngeal carcinoma is a common cancer in Southern China. Despite multiple genetic changes have been reported previously, limited information of NPC-associated oncogene is available. Since amplification is one of the major mechanisms in oncogene activation, a comprehensive characterization of common amplicons in human cancers is expected to facilitate the identification of the oncogenes involved in tumorigenesis. The aims of the present study is to define and characterize the common amplicons in NPC genome and then to identify NPC-associated oncogenes. / Or Yan Yan. / "July 2006." / Adviser: Kwok Wai Lo. / Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5715. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 179-201). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Genes identified by SAGE may serve as potential prognostic marker or therapeutic target. 14-3-3 sigma is a putative tumor suppressor and can be induced in response to DNA damage following irradiation, leading to cell cycle arrest in G2/M in human cancer cells. Our SAGE results revealed that 14-3-3 sigma expression is significantly downregulated in C666-1 cells. The study of 72 primary NPCs showed that an increased expression of 14-3-3 sigma was associated with a poorer clinical outcome in terms of shorter overall survival (OS; p=0.0297) and shorter disease free survival (DFS; p=0.042) using univariate analysis. Hence, 14-3-3 sigma may be used as an independent prognostic marker for NPC patients. / In conclusion, a NPC transcription profile has been successfully generated and several candidate NPC-associated genes have been identified by Serial Analysis of Gene Expression (SAGE) and NPC transcriptome map. These novel findings lead to better understanding of the molecular basis of NPC development and provide a foundation for discovery of new therapeutic strategies. / Nasopharyngeal carcinoma (NPC) is one of the most prevalent cancers among Southern Chinese. To better understand the genetic basis of this disease, Serial Analysis of Gene Expression (SAGE) was performed to investigate the transcriptional profiles of an EBV-positive NPC cell line (C666-1) and a normal NP outgrowth (NP4). A total of 102,059 SAGE tags were extracted in both libraries and 250 genes with 10-fold or more differential expression were found in NPC cells compared to normal NP cells. Eleven differentially expressed genes identified by SAGE were selected for confirmation using real time RT-PCR. The transcripts for 5 of the 11 genes, CD 74, Transcriptional intermediary factor 1, Ferritin 1, Claudin 4, and fatty acid synthase were overexpressed in NPC cells. Conversely, the remaining transcripts including Keratin 17, Keratin 5, S100 calcium-binding A2, Cystatin A, 14-3-3 sigma and Caveolin 1 were underexpressed in NPC cells. The aberrant expression of CD74, Claudin 4, Fatty acid synthase, 14-3-3 sigma, Caveolin 1 were further validated by immunohistochemistry on 20 NPC patients. / On the other hand, fatty acid synthase (FASN), a key enzyme for de novo lipogenesis, is a putative therapeutic target in treating NPC. Immunohistochemical studies showed upregulation of FASN in 20.8% (15/72) of the NPC cases compared with the adjacent normal NP epithelium. In addition, FASN expression also had prognostic significance in predicting the outcome of patients after radiotherapy, as high levels of FASN expression were associated with worse overall survival (OS, p=0.032) and disease free survival (DFS, p=0.002) in NPC patients. FASN inhibitors, such as C75 which inhibit cell growth via cell cycle arrest in G2/M phase, are potential chemotherapeutic agents in treating NPC. / The genome-wide quantitative analysis of gene expression by SAGE with matched chromosomal positions enables the construction of a transcriptome map of NPC. A total of 8 and 29 overexpressed and underexpressed gene clusters were observed, respectively. Some novel regions that have never been illustrated in previous reports such as amplification regions at 2p11.2-p25.1, 2q33-q37, 9q22-q34, 17p11.2-p13.2 and deletion regions at 1p12-p31.2, 1q25-q42.12, 2q21.3-q33, 8p21.1-p22, 9q33-q34.3, 10q23.3-q26.3, 12p13, 16p13, 17q23.2-q25, 19p13, 19q12-q13.2, 20p11-p13, 22q13, Xp11.2-p11.4, and Xq26-q28 were also identified. A candidate tumor suppressor gene named MEG3 has been found within an underexpressed region at 14q32.2 in the NPC transcriptome map. Our FISH analysis revealed that chromosome loss at 14q32 is associated with hypermethylation of MEG3 promoter region in 9/13 (75%) of NPC patients. Loss of imprinting is the major mechanism that governs the MEG3 expression. Moreover, transient transfection of one of the MEG3 isoforms (accession no. AF119863) could obviously inhibit cell colony formation of NPC cells. Taken together, MEG3 gene on chromosome 14q32.2 might act as a tumor suppressor in NPC. / Chan, Yat Yee. / "March 2008." / Adviser: Lo Kwok Wai. / Source: Dissertation Abstracts International, Volume: 70-03, Section: B, page: 1605. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (p. 196-225). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Chan Siu-chung Andrew. / "December 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 120-136). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Hui Wai Ying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 158-189). / Abstracts in English and Chinese. / Abstract / Acknowledgements / List of Tables / List of Figures / Table of Contents / Table of Contents / Chapter Chapter I: --- Introduction --- p.1 / Chapter I. --- Aim of Study --- p.1 / Chapter II. --- Literature Review --- p.3 / Chapter 1. --- Background --- p.3 / Chapter A. --- Epidemiology --- p.3 / Chapter B. --- Histopathology --- p.3 / Chapter C. --- Etiology --- p.4 / Chapter i. --- Environmental Factors --- p.5 / Chapter ii. --- Epstein-Barr Virus (EBV) Infection --- p.6 / Chapter iii. --- Genetic Factors --- p.9 / Chapter 2. --- Molecular Genetics of NPC --- p.11 / Chapter A. --- Genome-Wide Studies --- p.11 / Chapter i. --- Comparative Genomic Hybridization (CGH) --- p.11 / Chapter ii. --- Loss of Heterozygosity (LOH) Studies --- p.12 / Chapter iii. --- Homozygous Deletion Study --- p.12 / Chapter B. --- NPC-related Oncogenes and Tumor Suppressor Genes --- p.13 / Chapter i. --- Oncogenes --- p.13 / Chapter ii. --- Tumor Suppressor Genes --- p.14 / Chapter 3. --- Chromosome 14q and NPC --- p.19 / Chapter A. --- Tumor Suppressor Loci and Cancer-Related Genes on Chromosome14q --- p.20 / Chapter i. --- Tumor Suppressor Loci on Chromosome 14q --- p.20 / Chapter ii. --- Cancer-Related Genes on Chromosome 14q --- p.26 / Chapter 4. --- Chromosome 16q and NPC --- p.28 / Chapter A. --- Tumor Suppressor Loci and Candidate Tumor Suppressor genes on Chromosome16q --- p.28 / Chapter i. --- Tumor Suppressor Loci on Chromosome 16q --- p.28 / Chapter ii. --- Metastasis Suppressor Loci on Chromosome 16q --- p.34 / Chapter iii. --- Candidate Tumor Suppressor Genes on Chromosome 16q --- p.34 / Chapter Chapter II: --- Materials and Methods --- p.40 / Chapter I. --- Cell Lines and Xenografts --- p.40 / Chapter 1. --- Cell Lines --- p.40 / Chapter 2. --- Xenografts --- p.41 / Chapter 3. --- DNA Extraction --- p.42 / Chapter II. --- Patients and Biopsy Specimens --- p.44 / Chapter 1. --- Manual Microdissection --- p.44 / Chapter 2. --- Laser Captured Microdissection (LCM) --- p.46 / Chapter 3. --- DNA Extraction --- p.46 / Chapter III. --- Comprehensive Screening for Homozygous Deletion Regions on Chromosomes 14q32.12-32.33 and 16q23.1-24.3 in Human Cancers --- p.48 / Chapter 1. --- DNA of Human Cancer Cell Lines --- p.48 / Chapter 2. --- Sequence-Tagged Sites (STS) Markers --- p.48 / Chapter 3. --- Polymerase Chain Reaction (PCR) --- p.49 / Chapter IV --- . Investigation of Inactivation of Potential Tumor Suppressor Genes on Chromosome 14q32.12-32.33 and 16q23.1-24.3 --- p.58 / Chapter 1. --- Detection of Homozygous Deletion --- p.58 / Chapter 2. --- Expression Analysis --- p.58 / Chapter A. --- RNA Extraction --- p.58 / Chapter B. --- Reverse-Transcription (RT) PCR --- p.61 / Chapter i. --- DNase I Digestion --- p.62 / Chapter ii. --- First-strand cDNA Synthesis and RNase Digestion --- p.62 / Chapter iii. --- Reverse-Transcription (RT)-PCR --- p.63 / Chapter C. --- Real-Time RT PCR --- p.63 / Chapter 3. --- Methylation Analysis --- p.68 / Chapter A. --- Sodium Bisulfite Modification --- p.68 / Chapter B. --- Methylation-Specific PCR (MSP) --- p.69 / Chapter C. --- Bisulfite Sequencing --- p.70 / Chapter D. --- Combined Bisulfite Restriction Analysis (COBRA) --- p.75 / Chapter E. --- 5 -aza-2' -deoxycytidine Treatment --- p.76 / Chapter ChapterIII： --- Results --- p.78 / Chapter I. --- Comprehensive Screening for Homozygous Deletion Regions in Human Cancers --- p.78 / Chapter 1. --- Chromosome 14q32.12-3233 --- p.78 / Chapter 2. --- Chromosome 16q23.1-243 --- p.79 / Chapter II. --- Investigation of Inactivation of Potential Tumor Suppressor Genes in NPC --- p.86 / Chapter 1. --- Chromosome 14q --- p.86 / Chapter A. --- "WW Domain-Containing Protein, 45-kD （WW45)" --- p.86 / Chapter B. --- Apoptosis Stimulating Protein of p53（ASPP1) --- p.88 / Chapter 2. --- Chromosome 16q --- p.92 / Chapter A. --- WW Domain-Containing Oxidoreductase （WWOX) --- p.92 / Chapter i. --- Homozygous Deletion Screening of WWOX --- p.92 / Chapter ii. --- Expression of Aberrant Splicing Transcripts of WWOX in NPC --- p.94 / Chapter iii. --- Sequencing of WWOX Aberrant Transcripts --- p.95 / Chapter iv. --- Quantitative Analysis of WWOX Transcripts in NPC --- p.95 / Chapter v. --- Methylation Analysis --- p.99 / Chapter B. --- H-Cadherin (CDH13) --- p.102 / Chapter i. --- Analysis of H-cadherin Deletion on Cancer Cell Lines and Xenografts --- p.102 / Chapter ii. --- Expression Analysis of H-Cadherin by RT-PCR and Real-Time RT-PCR --- p.102 / Chapter iii. --- Analysis of Promoter Hypermethylation by Methylation-Specific PCR (MSP) and Bisulfite Sequencing in NPC Cell Lines and Xenografts --- p.104 / Chapter iv. --- Demethylation Study of H-Cadherin in C666-1 Cell Line --- p.105 / Chapter v. --- Methylation Analysis of H-Cadherin in Primary Tumors --- p.105 / Chapter vi. --- Methylation Analysis of H-Cadherin in Human Cancer Cell Lines --- p.106 / Chapter C. --- Myeloid Translocation Gene on Chromosome 16 (MTG16) --- p.113 / Chapter i. --- Deletion Analysis of MTG16 in Cancer Cell Lines and Xenografts --- p.113 / Chapter ii. --- Differential Expression of MTG16a and MTG16b Transcripts in NPC Cell Lines and Xenografts --- p.113 / Chapter iii. --- Methylation Analysis of MTG16b in NPC Cell Lines and Xenografts --- p.118 / Chapter iv. --- Sequencing of MTGl 6b RT-PCR Products --- p.119 / Chapter v. --- Demethylation Study of MTG16b in HK-1 Cell Line --- p.119 / Chapter vi. --- Promoter Methylation Analysis of MTG16b by MSP in Primary NPC and Cancer Cell Lines --- p.120 / Chapter Chapter IV: --- Discussion --- p.124 / Chapter I. --- Comprehensive Homozygous Deletion Screening of Chromosomes 14q32.12-32.33 and 16q23.1-24.3 in Human Cancer Cell Lines and Xenografts --- p.124 / Chapter II. --- Investigation of Candidate Tumor Suppressor Genes on Chromosome 14q in NPC --- p.128 / Chapter III. --- Alterations of Candidate Tumor Suppressor Genes on Chromosome 16q in NPC --- p.133 / Chapter 1. --- Expression of Aberrant Transcripts of WWOX in NPC --- p.133 / Chapter 2. --- Methylation-Associated Silencing of H-Cadherin and MTG16b in NPC --- p.140 / Chapter Chapter V: --- Conclusion --- p.154 / Chapter Chapter VI: --- References --- p.158

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.