Intratumor Diversity and Clonal Evolution in Cancer

Intratumor Diversity and Clonal Evolution in Cancer

1st Edition - September 29, 2011

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  • Editor: David Gisselsson
  • Hardcover ISBN: 9780123876881
  • eBook ISBN: 9780123877086

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This specialized volume of Advances in Cancer Research is dedicated to the complex and largely unexplored field of intratumor diversity, with respect to differences in both genotype and phenotype among cell populations within tumors.

Key Features

  • Unique subject matter: there are relatively few previous publications covering this complex topic, even though it has been a matter of much speculation ever since cancers were first studied under the microscope more than a century ago. This volume is an attempt to update the reader on novel findings as well as giving a historical perspective to the field. It thereby offers an excellent starting point for young scientists entering this field of research
  • Contributors: many of the contributors are renowned cancer researchers with long-term experience. To bring in new ideas to the field, these experienced authors have been blended with young bright minds who might provide novel starting points for solving old problems
  • Technical aspects: some chapters will be focused on specific techniques to address intratumor diversity and will therefore be helpful for colleagues wanting to broaden their technical expertise


Researchers and students in the basic and clinical sciences of cancer biology and oncology, plus related areas in genetics, immunology, pharmacology, cell biology, and molecular biology

Table of Contents

  • Intratumor Diversity and Clonal Evolution in Cancer—A Skeptical Standpoint

    I. Introduction


    Role of Telomere Dysfunction in Genetic Intratumor Diversity

    I. Introduction

    II. Chromosome End Protection: The Shelterin Complex

    III. Telomere Maintenance, Cell Proliferation, and Telomere Uncapping

    IV. Telomeres, checkpoints, and cancer

    V. Telomere Uncapping as a Source of Genomic Instability

    VI. Shortening Telomeres in Aged Human Cells

    VII. Summary


    How Mitotic Errors Contribute to Karyotypic Diversity in Cancer

    I. Introduction

    II. Intratumor Diversity at the Karyotypic Level

    III. How Mitotic Errors Contribute to the Karyotypic Diversity of Cancer Cells

    IV. Conclusion


    Nuclear Remodeling as a Mechanism for Genomic Instability in Cancer

    I. Introduction

    II. Imaging Techniques Employed in Nuclear Remodeling Studies

    III. Myc-Dependent Genomic Instability and Nuclear Remodeling

    IV. Nuclear Remodeling and Genomic Instability in Primary Tumors

    V. Models of Genomic Instability Occurring within the Nuclear Space

    VI. Conclusions


    Cytogenetic Analysis of Tumor Clonality

    I. Introduction

    II. Cytogenetic assessment of clonal composition of pancreatic and large bowel tumors

    III. Cytogenetic assessment of breast tumor clonality

    IV. Cytogenetic assessment of urinary bladder tumor clonality

    V. Monoclonal versus polyclonal tumorigenesis: Is the jury still out?

    Genotyping Techniques to Address Diversity in Tumors

    I. Introduction

    II. The Basic Principles Of SNP Array Platforms And SNP Array Data Interpretation

    III. Whole Genome Genotyping Of Tumor Samples

    IV. WGG Analyses Of Complex And Heterogeneous Cell Populations

    V. Concluding Remarks

    Prostate Cancer as a Model System for Genetic Diversity in Tumors

    I. Incidence of prostate cancer

    II. Clinical heterogeneity of prostate cancer

    III. Pathology of the normal prostate and prostate cancer

    IV. Prostate cancer oncogenomics

    V. Discovery oftmprss2:ets fusion genes in prostate cancer

    VI. Frequency of tmprss2:ets gene fusions in prostate cancer

    VII. Androgen driven tmprss2 gene fusions

    VIII. Ets transcription factors

    IX. Detection of fusion gene rearrangements by fish

    X. Loss of pten in prostate cancer

    XI. Genomic alterations in prostate cancer preneoplasia

    XII. Genetic diversity generated by telomere loss in preneoplasia

    XIII. Chromosomal instability and genetic diversity in prostate cancer

    XIV. Multifocal genotypic heterogeneity of prostate cancer

    XV. Involvement of the stroma in the disease process

    XVI. Stem cell origins for prostate cancer

    XVII. Prospective: emerging insights from prostate cancer genomic sequencing


    Evolutionary Mechanisms and Diversity in Cancer

    I. Introduction

    II. A Brief Review of Cancer Evolutionary Studies

    III. Genetic Organization and Diversity

    IV. Multiple Levels of Control Systems are Essential for Biological Functions

    V. The Pattern of Evolutionary Dynamics of Somatic Cell Evolution

    VI. The Evolutionary Mechanism of Cancer and its Medical Implications


    Cancer Stem Cells in Tumor Heterogeneity

    I. Introduction

    II. A brief introduction to models of tumor development

    III. Evidence for a role of cancer stem cells in phenotypic tumor cell heterogeneity

    IV. Clues from metastatic and recurring lesions

    V. Cancer stem cells and endothelial/stromal differentiation

    VI. Cancer stem cells in angiogenesis

    VII. Cancer stem cells in heterogeneity of the therapeutic response

    VIII. Unresolved issues regarding the cancer stem cell model in tumor heterogeneity

    IX. Future directions


    Cancer: Beyond Speciation

    I. Introduction

    II. How To “Understand” Cancer

    III. “Conventional Wisdom”: The Darwinian View of Cancer

    IV. Alternative Interpretations of Cancer

    V. Cancer as Speciation: Implications for Biology and Therapy

    VI. Beyond Speciation: The Nature of Cancer

    VII. The Nature of Cancer: A Trait-Based Inferential Approach

    VIII. Resistance to Therapy: The Long Arm of The Proterozoic

    IX. Is There an Answer?

    X. What Form of Life?

Product details

  • No. of pages: 368
  • Language: English
  • Copyright: © Academic Press 2011
  • Published: September 29, 2011
  • Imprint: Academic Press
  • Hardcover ISBN: 9780123876881
  • eBook ISBN: 9780123877086

About the Editor

David Gisselsson

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