Intratumor Diversity and Clonal Evolution in Cancer

Intratumor Diversity and Clonal Evolution in Cancer—A Skeptical Standpoint

I. Introduction

Acknowledgment

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

Acknowledgments

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

Acknowledgments

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

Acknowledgments

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

Acknowledgment

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

Acknowledgments

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

Acknowledgments

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?