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Detection of epidermal growth factor receptor mutations in the plasma of non-small-cell lung cancer patients. / 肺癌病人的血漿樣本中上皮細胞生長因素接收器(EGFR)基因突變的檢測 / Fei ai bing ren de xue jiang yang ben zhong shang pi xi bao sheng zhang yin su jie shou qi (EGFR) ji yin tu bian de jian ce

Yung, Kam Fai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 107-129). / Abstracts in English and Chinese. / ABSTRACT --- p.ii / 摘要 --- p.iv / ACKNOWLEDGEMENTS --- p.vi / TABLE OF CONTENTS --- p.vii / PUBLICATION --- p.ix / LIST OF TABLES --- p.x / LIST OF FIGURES --- p.xi / LIST OF ABBREVIATIONS --- p.xii / Chapter SECTION I: --- BACKGROUND --- p.1 / Chapter CHAPTER 1: --- "The biology, diagnostics and management of lung cancer" --- p.2 / Chapter 1.1 --- "Basic biology, classification and diagnostics" --- p.2 / Chapter 1.1.1 --- Epidemiology and etiology of lung cancer --- p.2 / Chapter 1.1.2 --- Clinical Presentation and Diagnostics of Lung Cancer --- p.3 / Chapter 1.2 --- Treatment of lung cancer --- p.9 / Chapter 1.2.2 --- Radiotherapy --- p.10 / Chapter 1.2.3 --- Chemotherapy --- p.11 / Chapter CHAPTER 2: --- Epidermal Growth Factor Receptor Mutations in Lung Cancer --- p.13 / Chapter 2.1 --- The Epidermal Growth Factor Receptor --- p.13 / Chapter 2.2 --- Overexpression of EGFR in NSCLC --- p.14 / Chapter 2.3 --- The development of EGFR inhibitors --- p.15 / Chapter 2.3.1 --- Monoclonal Antibodies --- p.16 / Chapter 2.3.2 --- Small-molecule inhibitors --- p.17 / Chapter 2.3.2.1 --- Gefitinib --- p.17 / Chapter 2.3.2.2 --- Erlotinib --- p.19 / Chapter 2.3.2.3 --- Other small-molecule inhibitors --- p.20 / Chapter 2.4 --- Mutations of EGFR in NSCLC --- p.21 / Chapter 2.4.1 --- Activating Mutations conferring sensitivity to tyrosine kinase inhibitors --- p.21 / Chapter 2.4.2 --- Secondary mutations associated with resistance to tyrosine kinase inhibitors --- p.23 / Chapter 2.5 --- EGFR gene amplification --- p.24 / Chapter 2.6 --- Detection of EGFR mutations --- p.25 / Chapter 2.7 --- Aim of the thesis --- p.31 / Chapter SECTION II: --- DETECTION OF EGFR MUTATIONS IN TUMOR AND PLASMA SAMPLES BY MASS SPECTROMETRY AND DIGITAL PCR --- p.33 / Chapter CHAPTER 3: --- Detection of EGFR mutations by mass spectrometric methods --- p.34 / Chapter 3.1 --- Introduction --- p.34 / Chapter 3.1.1 --- Principles of Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) --- p.34 / Chapter 3.1.2 --- The MassARRAY Homogenous MassEXTEND (hME) assay --- p.35 / Chapter 3.1.3 --- The Single-Allele Base Extension Reaction (SABER) and the Allele-Specific Base Extension Reaction (ASBER) --- p.36 / Chapter 3.2 --- Materials and Methods --- p.36 / Chapter 3.2.1 --- The protocol for the detection of EGFR exon 21 point mutation by Mass Spectrometric Methods --- p.37 / Chapter 3.3 --- Results --- p.42 / Chapter 3.4 --- Discussion --- p.49 / Chapter CHAPTER 4: --- Evaluation of the detection limit and sensitivity of the digital PCR assays --- p.51 / Chapter 4.1 --- Introduction --- p.51 / Chapter 4.1.1 --- The theoretical basis of digital PCR quantification and the relationship with the Poisson distribution --- p.51 / Chapter 4.1.2 --- Assessment of Assay Detection Limit --- p.54 / Chapter 4.1.3 --- Comparing Digital PCR with sequencing after conformation sensitive gel electrophoresis (CSGE) --- p.59 / Chapter 4.2 --- Materials and Methods --- p.59 / Chapter 4.2.1 --- Design of digital PCR assay for the detection of EGFR exon21 L858R point mutation --- p.59 / Chapter 4.2.2 --- Design of digital PCR assay for the detection of EGFR exon19 deletion --- p.60 / Chapter 4.2.3 --- The protocols of digital PCR assays for EGFR mutation detection --- p.64 / Chapter 4.2.4 --- Single molecule detection test --- p.65 / Chapter 4.2.5 --- Artificial mixtures of mutant and wild-type DNA --- p.66 / Chapter 4.2.6 --- Sequencing after CSGE --- p.66 / Chapter 4.3 --- Results --- p.67 / Chapter 4.3.1 --- Results of the single molecule detection test and artificial mixture analysis --- p.67 / Chapter 4.3.2 --- Results of CSGE and sequencing compared with digital PCR --- p.73 / Chapter 4.4 --- Discussion --- p.75 / Chapter CHAPTER 5: --- Detection of EGFR mutations in prospectively collected tumor samples of NSCLC patients --- p.77 / Chapter 5.1 --- Introduction --- p.77 / Chapter 5.2 --- Materials and Methods --- p.78 / Chapter 5.2.1 --- Sample preparation and DNA extraction of tumor tissues --- p.78 / Chapter 5.3 --- Results --- p.79 / Chapter 5.4 --- Discussion --- p.82 / Chapter CHAPTER 6: --- Detection of EGFR mutations in prospectively collected plasma samples of NSCLC patients --- p.85 / Chapter 6.1 --- Introduction --- p.85 / Chapter 6.2 --- Materials and Methods --- p.87 / Chapter 6.2.1 --- Sample preparation and DNA extraction of plasma samples --- p.87 / Chapter 6.3 --- Results --- p.88 / Chapter 6.3.1 --- Digital PCR analysis of EGFR mutations in plasma samples of NSCLC patient --- p.88 / Chapter 6.3.2 --- Variations in plasma EGFR mutation concentration after TKI treatment --- p.93 / Chapter 6.4 --- Discussion --- p.96 / Chapter SECTION III: --- CONCLUDING REMARKS --- p.100 / Chapter CHAPTER 7: --- Conclusion and future perspectives --- p.101 / Chapter 7.1 --- Mass spectrometric analysis --- p.101 / Chapter 7.2 --- Microfluidics Digital PCR --- p.102 / Chapter 7.3 --- Future perspectives --- p.105 / References --- p.107

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_326655
Date January 2009
ContributorsYung, Kam Fai., Chinese University of Hong Kong Graduate School. Division of Chemical Pathology.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, bibliography
Formatprint, xiii, 128 leaves : ill. ; 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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