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DNA methylation studies in multiple myeloma.

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

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_324726
Date January 2004
ContributorsLeung, Sau Ching., Chinese University of Hong Kong Graduate School. Division of Anatomical and Cellular Pathology.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, bibliography
Formatprint, xvii, 165 leaves : ill. (some col.) ; 30 cm.
RightsUse of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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