The widespread occurance of cancer and its apparent lack of a cause has led to a plethora of myths spanning from a "cancer personality" in the 1970's to mobile phones today. The dissertation introduces some of the theoretical principles of cancer which lifts the veil on the mysteries surrounding its causes. The central issue addressed is whether genetic instability above the background level is necessary to account for the levels of cancer seen. In doing so, it touches on the idea that we are all born with mutations - from the very first division at the embryonic stage we begin acquiring them. This occurs even in a perfect environment without mutagens or any environmental stressors. The common conception, of the cells working together for a common goal is reversed. The body can be viewed as a vast community of selfish cells which are constantly competing for resources in a process analogous to Darwinian natural selection.
Evolution at the organism level has resulted in a comprehensive disciplinary system to keep the masses in check. Any individual which
hints at crossing out of line is sentenced to the biochemical equivalent of imprisonment or the death sentence. However despite the organism's iron tight grip on the individual cell, it is clear that we all carry the prerequisites of cancer around with us. We will all be diagnosed with "cancer" at some point, the reason it only kills a third is that most die of something else first. Even if we live a perfect life without any disease - there is always the self which is imperfect. This dissertation explains in detail how we are gaining a deeper understanding which offers the hope that in the near future we will no longer need to live in fear of the unknown.
Inhaltsverzeichnis (Table of Contents)
- Introduction
- How many mutations are required to produce a human cancer cell?
- Sequence data
- Epidemiology
- In vitro data
- Histopathology
- Is genetic instability necessary to acquire sufficient mutations?
- The mutator phenotype hypothesis
- Arguments which undermine the calculations' assumptions
- Clonal evolution and natural selection
- Arguments for the calculations validity
- Tissue Biology
- Epigenetics
- CpG island promoter hypermethylation
- Global CpG hypomethylation
- Does genetic instability accelerate tumour progression?
- Cell clone ecology hypothesis
- Mathematical assessment
- Lab based test
- Clinical data
- Sequence Data
- Implications for therapy
- Conclusion
Zielsetzung und Themenschwerpunkte (Objectives and Key Themes)
This work aims to investigate the role of genetic instability in tumor progression by exploring whether it is a necessary condition for acquiring the required number of mutations and whether it accelerates tumor evolution. The text aims to provide a comprehensive overview of the debate surrounding the necessity of genetic instability for tumor development, drawing on various theoretical models and experimental evidence.
- The number of mutations required for tumor development
- The role of genetic instability in acquiring sufficient mutations
- The mutator phenotype hypothesis and its arguments for and against
- The impact of genetic instability on tumor progression and evolution
- The influence of tissue biology and epigenetics on tumor development
Zusammenfassung der Kapitel (Chapter Summaries)
The introduction establishes the importance of understanding the mechanisms behind tumor progression and outlines the key question of whether genetic instability is a necessary component. It discusses the six fundamental hallmarks of cancer as proposed by Hanahan and Weinberg (2000) and how genetic instability might contribute to their development.
The chapter "How many mutations are required to produce a human cancer cell?" examines the evidence from various sources, including sequence data, epidemiology, in vitro studies, and histopathology. It aims to establish whether the background mutation rate is sufficient to produce the required number of mutations for tumorigenesis.
The chapter "Is genetic instability necessary to acquire sufficient mutations?" delves into the mutator phenotype hypothesis and its arguments. It explores the contrasting perspectives on the role of natural selection and genetic instability in tumor evolution. It also addresses the limitations of the multistep Darwinian model and how advancements in tissue biology suggest a more complex picture of tumor development.
The chapter "Tissue Biology" introduces the concept of epigenetics and its potential contribution to tumorigenesis. It examines the role of CpG island promoter hypermethylation and global CpG hypomethylation in tumor development. It discusses how epigenetic alterations may provide an alternative route for initiating and sustaining tumor progression.
The chapter "Does genetic instability accelerate tumour progression?" explores the cell clone ecology hypothesis and its relevance to understanding tumor evolution. It discusses the implications of a limited population undergoing selection at the tip of a cellular hierarchy. The chapter further delves into mathematical assessments, lab-based tests, and clinical data to investigate the impact of genetic instability on tumor progression.
Schlüsselwörter (Keywords)
The primary keywords and focus topics include genetic instability, tumor progression, mutator phenotype hypothesis, Darwinian natural selection, cell clone ecology hypothesis, epigenetics, CpG island promoter hypermethylation, global CpG hypomethylation, and theoretical models. The text explores the interplay of these factors in shaping tumor development and the implications for cancer therapy and prevention strategies.
- Quote paper
- Pascal Kaufmann (Author), 2011, How many mutations are required to produce a human cancer cell?, Munich, GRIN Verlag, https://www.grin.com/document/168293
