Page 9 - 20dynamics of cancer

viii CONTENTS
4 History of Theories 59

4.1 Origins of Multistage Theory 61
4.2 A Way to Test Multistage Models 65
4.3 Cancer Is a Genetic Disease 69
4.4 Can Normal Somatic Mutation
Rates Explain Multistage
Progression? 71
4.5 Clonal Expansion of
Premalignant Stages 74
4.6 The Geometry of Cell Lineages 76
4.7 Hypermutation, Chromosomal
Instability, and Selection 78
4.8 Epigenetics: Methylation and
Acetylation 79
4.9 Summary 80

PART II: DYNAMICS

5 Progression Dynamics 85

5.1 Background 86
5.2 Observations to Be Explained 89
5.3 Progression Dynamics through
Multiple Stages 90
5.4 Why Study Quantitative
Theories? 93
5.5 The Basic Model 93
5.6 Technical Definitions of
Incidence and Acceleration 94
5.7 Summary 95

6 Theory I 96
6.1 Approach 97
6.2 Solution with Equal Transition
Rates 97
6.3 Parallel Evolution within Each
Individual 100
6.4 Unequal Transition Rates 103