DNA methylation studies in multiple myeloma.

• Other Authors: Leung, Sau Ching.
• Format: Others
• Language: English; Chinese
• Published: 2004
• Subjects: DNA > Methylation; Multiple myeloma; DNA Methylation; Multiple Myeloma
• Online Access: http://library.cuhk.edu.hk/record=b5891982; http://repository.lib.cuhk.edu.hk/en/item/cuhk-324726

Leung Sau Ching. === Thesis submitted in: October 2003. === Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. === Includes bibliographical references (leaves 142-165). === Abstracts in English and Chinese. === Acknowledgments --- p.ii === Abstract (English Version) --- p.iii === Abstract (Chinese Version) --- p.vi === Table of Contents --- p.viii === List of Tables --- p.xii === List of Figures --- p.xiii === List of Abbreviations --- p.xv === Chapter CHAPTER 1 --- INTRODUCTION --- p.1 === Chapter 1.1 --- Multiple Myeloma (MM) --- p.1 === Chapter 1.1.1 --- Epidemiology --- p.3 === Chapter 1.1.2 --- Clinical and Pathologic Features of MM --- p.3 === Chapter 1.1.3 --- Diagnosis and Staging --- p.4 === Chapter 1.1.4 --- Prognosis --- p.6 === Chapter 1.1.5 --- Treatment --- p.7 === Chapter 1.2 --- Molecular Abnormalities of MM --- p.8 === Chapter 1.2.1 --- Genetic Alterations: Chromosomal Aberrations --- p.8 === Chapter 1.2.2 --- Genetic Alterations: Ras Mutations --- p.11 === Chapter CHAPTER 2 --- LITERATURE REVIEW --- p.12 === Chapter 2.1 --- Epigenetic Alterations: DNA Methylation --- p.12 === Chapter 2.1.1 --- Characteristics of CpG Island --- p.14 === Chapter 2.1.2 --- Mechanism of Methylation-Related Gene Silencing --- p.14 === Chapter 2.1.3 --- DNA Methylation Is Important for Normal Cellular Functions --- p.17 === Chapter 2.1.4 --- DNA Methylation Changes in Cancer Cells --- p.17 === Chapter 2.1.5 --- Global DNA Hypomethylation --- p.18 === Chapter 2.1.6 --- Regional DNA Hypermethylation --- p.20 === Chapter 2.1.6.1 --- De Novo Methylation --- p.21 === Chapter 2.1.6.2 --- DNA Hypermethylation Acts as a Third Pathway to Loss of Function in Carcinogenesis --- p.21 === Chapter 2.1.6.3 --- DNA Hypermethylation Contributes to Tumorigenesis --- p.25 === Chapter 2.1.6.4 --- Methodologies in the Study of DNA Hypermethylation --- p.26 === Chapter 2.1.6.5 --- Single Gene Hypermethylation --- p.28 === Chapter 2.1.6.6 --- Multiple Gene Hypermethylation --- p.30 === Chapter 2.1.6.7 --- Potential Clinical Applications of DNA Hypermethylation --- p.36 === Chapter 2.1.6.7.1 --- Tumor Cells Detection by 5'CpG Island Hypermethylation --- p.37 === Chapter 2.1.6.7.2 --- Prognostic and Predictive Significances of DNA Hypermethylation --- p.39 === Chapter 2.1.6.7.3 --- Therapeutic Intervention of CpG island Hypermethylation --- p.40 === Chapter 2.2 --- DNA Hypermethylation in MM and MGUS --- p.43 === Chapter 2.3 --- Six-Genes Panel for the Hypermethylation Study --- p.45 === Chapter 2.3.1 --- Apoptotic Pathway: DAP-kinase --- p.45 === Chapter 2.3.2 --- Retinoid Signaling Pathway: RARβ --- p.50 === Chapter 2.3.3 --- Angiogenic Pathway: THBS-1 --- p.52 === Chapter 2.3.4 --- Cell cycle Regulatory Pathway: pl6 and p15 --- p.57 === Chapter 2.3.5 --- Ras Signaling Pathway: RASSF1A --- p.62 === Chapter CHAPTER 3 --- BACKGROUND OF STUDY --- p.67 === Chapter 3.1 --- Rationale --- p.67 === Chapter 3.2 --- Hypothesis --- p.69 === Chapter 3.3 --- The Objectives of Study --- p.70 === Chapter CHAPTER 4 --- MATERIALS AND METHODS --- p.71 === Chapter 4.1 --- Culture of Human Multiple Myeloma (MM)-derived Cell Lines --- p.71 === Chapter 4.2 --- Demethylation Treatment --- p.72 === Chapter 4.3 --- Patient and Control Samples --- p.72 === Chapter 4.4 --- DNA Extraction --- p.73 === Chapter 4.5 --- MS-PCR --- p.73 === Chapter 4.6 --- Plasma Cell Isolation --- p.77 === Chapter 4.7 --- RNA Extraction and RT-PCR --- p.78 === Chapter 4.8 --- Statistics --- p.82 === Chapter CHAPTER 5 --- RESULTS --- p.84 === Chapter 5.1 --- Patient Characteristics --- p.84 === Chapter 5.2 --- Single Gene Hypermethylation --- p.87 === Chapter 5.2.1 --- Normal PB Did Not Show Methylation --- p.87 === Chapter 5.2.2 --- DNA Hypermethylation in Human MM-derived Cell Lines --- p.87 === Chapter 5.2.3 --- DNA Hypermethylation in Primary MM --- p.89 === Chapter 5.3 --- Demethylation Treatment --- p.93 === Chapter 5.4 --- Concurrent Hypermethylation --- p.96 === Chapter 5.5 --- Statistical Analyses of Primary MM --- p.101 === Chapter 5.5.1 --- Statistical Analyses Between Single Gene Hypermethylation and Clinical Parameters (Categorical) --- p.101 === Chapter 5.5.2 --- Statistical Analyses Between Single Gene Hypermethylation and Clinical Parameters (Non-Categorical) --- p.101 === Chapter 5.5.3 --- Survival Analyses of Single Gene Hypermethylation --- p.105 === Chapter 5.5.4 --- Correlation Analyses of Concurrent Hypermethylation --- p.107 === Chapter 5.5.5 --- Correlation Analyses Between Concurrent Hypermethylation and Clinical Parameters --- p.107 === Chapter CHAPTER 6 --- DISCUSSION --- p.110 === Chapter 6.1 --- Involvement of Cellular Pathways by Hypermethylation --- p.111 === Chapter 6.1.1 --- Apoptotic Pathway: DAP-kinase and RARβ --- p.111 === Chapter 6.1.2 --- "Cell Cycle Regulatory Pathway: p16, p15 and RASSF1A" --- p.113 === Chapter 6.1.3 --- Angiogenic Pathway: THBS-1 --- p.117 === Chapter 6.2 --- Hypermethylation-Associated Gene Silencing --- p.119 === Chapter 6.3 --- Hypermethylation in Cell Lines and Primary MM --- p.120 === Chapter 6.4 --- Concurrent Hypermethylation --- p.122 === Chapter 6.4.1 --- DNA Hypermethylation is Common in MM --- p.122 === Chapter 6.4.2 --- Extent of Hypermethylation --- p.123 === Chapter 6.4.3 --- Involvement of Cellular Pathways by DNA Hypermethylation --- p.124 === Chapter 6.4.4 --- Concurrent p16 and DAP-kinase Hypermethylation --- p.126 === Chapter 6.5 --- Clinical Applications of DNA Hypermethylation --- p.129 === Chapter 6.5.1 --- Methylation As Tumor Markers for MM --- p.129 === Chapter 6.5.2 --- Prognostic Implications of DNA Hypermethylation in MM --- p.130 === Chapter 6.5.3 --- Correlations Between DNA Hypermethylation and Clinical Parameters --- p.131 === Chapter 6.6 --- MS-PCR --- p.136 === Chapter CHAPTER 7 --- CONCLUSION --- p.137 === Chapter CHAPTER 8 --- FURTHER STUDIES --- p.140 === References --- p.142