Cancer: Principles and Practice of Oncology Primer of Molecular Biology in Cancer

Höfundar: Vincent T. DeVita; Theodore S. Lawrence; Steven A. Rosenberg (Útgáfa: 3)
Cancer: Principles and Practice of Oncology Primer of Molecular Biology in Cancer

Kaup valmöguleikar

Recent scientific advances have revolutionized cancer research and practice, creating a body of molecular biology information that is important to research scientists and clinical oncologists alike. Cancer: Principles and Practice of Oncology: Primer of the Molecular Biology of Cancer, 3rd Edition, keeps you up to date with all that’s new in this rapidly changing field. Derived from DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology – widely regarded as the definitive clinical reference in oncology – the third edition of this popular Primer provides a single-volume, highly focused reference on every important frontier in the molecular biology of cancer.

Nánar um bókina

Útgefandi
Wolters Kluwer Health
ISBN
9781975149147
Print ISBN
9781975149116
Format
ePub
Útgáfa
3
Höfundar
Vincent T. DeVita; Theodore S. Lawrence; Steven A. Rosenberg
Tungumál
English
Útgefið
2020-01-22
Prent takmörkun á líftíma
10
Prent takmörkun
2
Afritunar takmörkun
2

Kaflar

  • Contributors
  • PART I: Principles of Molecular Oncology
  • 1. The Cancer Genome
  • Yardena Samuels, Alberto Bardelli, Yochai Wolf, and Carlos López-Otin
  • Introduction
  • Cancer Genes and Their Mutations
  • Identification of Cancer Genes
  • Cancer Gene Discovery by Sequencing Candidate Gene Families
  • Mutational Analysis of Exomes Using Sanger Sequencing
  • Next-Generation Sequencing and Cancer Genome Analysis
  • Whole-Genome Analysis Utilizing Second-Generation Sequencing
  • Whole-Exome Analysis Utilizing Second-Generation Sequencing
  • Somatic Alteration Classes Detected by Cancer Genome Analysis
  • Pathway-Oriented Models of Cancer Genome Analysis
  • Passenger and Driver Mutations
  • Networks of Cancer Genome Projects
  • The Genomic Landscape of Cancers
  • Single-Cell Genomics
  • Integrative Analysis of Cancer Genomics
  • Immunogenomics
  • The Cancer Genome and the New Taxonomy of Tumors
  • Liquid Biopsies as a Diagnosis Tool
  • Clinical Applications of Liquid Biopsies
  • Cancer Genomics and Drug Resistance
  • Perspectives of Cancer Genome Analysis
  • Acknowledgments
  • 2. Molecular Methods in Cancer
  • Larissa V. Furtado, Jay L. Hess, and Bryan L. Betz
  • Applications of Molecular Diagnostics in Oncology
  • Biomarker Genetics
  • Use of Biomarkers in Diagnosis
  • Use of Biomarkers in Prognosis
  • Use of Biomarkers in Predicting Response to Therapy
  • Use of Biomarkers in Therapeutic Disease Monitoring
  • Use of Biomarkers in Risk Assessment and Cancer Prevention
  • The Clinical Molecular Diagnostics Laboratory: Rules and Regulations
  • Specimen Requirements for Molecular Diagnostics
  • Molecular Diagnostics Testing Process
  • Targeted Mutation Analysis Methods
  • Polymerase Chain Reaction
  • Real-time Polymerase Chain Reaction
  • Reverse-Transcription Polymerase Chain Reaction
  • Allele-Specific Polymerase Chain Reaction
  • Fragment Analysis
  • Sanger Sequencing
  • Pyrosequencing
  • Methylation Analysis
  • Microsatellite Instability Analysis/Assessment of Mismatch Repair Deficiency
  • Fluorescence In Situ Hybridization
  • Whole-Genome Analysis Methods
  • Next-Generation Sequencing
  • Genomic Microarrays
  • Expression Panels
  • Immunohistochemistry for Tumor Biomarkers
  • PD-L1
  • ALK and ROS1
  • BRAFV600E
  • Cell-Free DNA Technologies
  • 3. Hallmarks of Cancer: An Organizing Principle for Cancer Medicine
  • Douglas Hanahan and Robert A. Weinberg
  • Introduction
  • Hallmark Capabilities, In Essence
  • Sustaining Proliferative Signaling
  • Somatic Mutations Activate Additional Downstream Pathways
  • Disruptions of Negative-Feedback Mechanisms that Attenuate Proliferative Signaling
  • Excessive Proliferative Signaling Can Trigger Cell Senescence
  • Evading Growth Suppressors
  • Mechanisms of Contact Inhibition and Its Evasion
  • Corruption of the Transforming Growth Factor β Pathway Promotes Malignancy
  • Resisting Cell Death
  • Autophagy Mediates Both Tumor Cell Survival and Death
  • Necrosis Has Proinflammatory and Tumor-Promoting Potential
  • Enabling Replicative Immortality
  • Reassessing Replicative Senescence
  • Delayed Activation of Telomerase May Both Limit and Foster Neoplastic Progression
  • Inducing Angiogenesis
  • Gradations of the Angiogenic Switch
  • Endogenous Angiogenesis Inhibitors Present Natural Barriers to Tumor Angiogenesis
  • Pericytes Are Important Components of the Tumor Neovasculature
  • A Variety of Bone Marrow–Derived Cells Contribute to Tumor Angiogenesis
  • Activating Invasion and Metastasis
  • The Epithelial-to-Mesenchymal Transition Program Broadly Regulates Invasion and Metastasis
  • Heterotypic Contributions of Stromal Cells to Invasion and Metastasis
  • Plasticity in the Invasive Growth Program
  • Distinct Forms of Invasion May Underlie Different Cancer Types
  • The Daunting Complexity of Metastatic Colonization
  • Reprogramming Energy Metabolism
  • Evading Immune Destruction
  • Two Ubiquitous Characteristics Facilitate the Acquisition of Hallmark Capabilities
  • An Enabling Characteristic: Genome Instability and Mutation
  • An Enabling Characteristic: Tumor-Promoting Inflammation
  • The Constituent Cell Types of the Tumor Microenvironment
  • Cancer-Associated Fibroblasts
  • Endothelial Cells
  • Pericytes
  • Immune Inflammatory Cells
  • Stem and Progenitor Cells of the Tumor Stroma
  • Heterotypic Signaling Orchestrates the Cells of the Tumor Microenvironment
  • Coevolution of the Tumor Microenvironment During Carcinogenesis
  • Cancer Cells, Cancer Stem Cells, and Intratumoral Heterogeneity
  • Therapeutic Targeting of the Hallmarks of Cancer
  • Conclusion and a Vision for the Future
  • Acknowledgment
  • 4. Oncogenic Viruses
  • Christopher B. Buck, Lee Ratner, and Giovanna Tosato
  • Principles of Tumor Virology
  • Papillomaviruses
  • History
  • Tissue Tropism and Gene Functions
  • Human Papillomavirus Vaccines
  • Oropharyngeal Cancer
  • Nonmelanoma Skin Cancer
  • Bladder Cancer
  • Polyomaviruses
  • History
  • BK Polyomavirus
  • Merkel Cell Polyomavirus
  • Other Human Polyomaviruses
  • Epstein-Barr Virus
  • History
  • Epstein-Barr Virus Life Cycle
  • Lymphomas
  • Carcinomas
  • Prevention and Treatment
  • Kaposi Sarcoma Herpesvirus
  • History and Epidemiology
  • Kaposi Sarcoma–Associated Herpesvirus in Kaposi Sarcoma
  • Lymphoproliferative Disorders
  • Animal and Human Retroviruses
  • Human T-Cell Leukemia Virus Epidemiology
  • Human T-Cell Leukemia Virus Molecular Biology
  • Clinical Characteristics and Treatment of Human T-lymphotropic Virus 1–Associated Malignancies
  • Hepatitis Viruses
  • Hepatitis B Virus
  • Hepatitis C Virus
  • Hepatitis Virus Pathogenesis
  • Clinical Characteristics and Treatment of Hepatitis Virus–Associated Malignancies
  • Conclusion
  • 5. DNA Repair in Normal and Cancer Cells
  • Meredith A. Morgan and Theodore S. Lawrence
  • Introduction
  • Radiation-Induced DNA Damage
  • Cellular Responses to Radiation-Induced DNA Damage
  • Cell Cycle Checkpoint Pathways
  • DNA Repair
  • Metabolism
  • Innate Immune Response
  • Chromosome Aberrations Result from Faulty DNA Double-Strand Break Repair
  • Membrane Signaling
  • The Effect of Radiation on Cell Survival
  • In Vivo Survival Determination of Normal Tissue Response to Radiation
  • In Vivo Determination of Tumor Response to Radiation
  • Factors That Affect Radiation Response
  • The Fundamental Principles of Radiobiology
  • Dose-Rate Effects
  • Relative Biologic Effectiveness
  • Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy
  • Cell Cycle
  • Tumor Oxygenation
  • Immune Response
  • Genetic Signatures
  • Drugs That Affect Radiation Sensitivity
  • Antimetabolites
  • Platinums and Temozolomide
  • Taxanes
  • Molecularly Targeted Agents
  • Immunotherapy
  • Radiation Protection
  • 6. Microbiome and Cancer
  • Giorgio Trinchieri
  • Introduction
  • Cancer as a Disease of the Metaorganism
  • Bacteria as Cause of Cancer
  • Helicobacter pylori and Stomach Cancer
  • Colorectal Cancer
  • Tumors in Tissues Not Directly Colonized by the Microbiota
  • The Microbiota Modulates Cancer-Predisposing Conditions and Comorbidity
  • Bacteria as Cancer Drugs
  • Microbiota and Drug Metabolism
  • Microbiota and Chemotherapy
  • Microbiota and Immunotherapy
  • Immune Checkpoint Blockers: Anti-CTLA-4
  • Immune Checkpoint Blockers: Anti-PD-1/PD-L1
  • Looking Forward
  • 7. Precision Medicine in Oncology
  • James H. Doroshow
  • Introduction
  • Approach to Precision Medicine in Oncology
  • Next-Generation DNA Sequencing for Precision Oncology
  • Broadening the Spectrum of Molecular Characterization
  • Preclinical Models to Inform Precision Oncology
  • Role of Molecular Pharmacodynamics and Diagnostics in Precision Oncology
  • Human Biospecimens for Molecular Characterization
  • Molecular Pharmacodynamics in Precision Oncology
  • Predictive Diagnostic Assays
  • Precision Oncology Clinical Trials and Trial Designs
  • Imaging and Precision Oncology
  • Precision Prevention
  • Future Prospects
  • 8. Cancer Immunotherapy
  • Jeffrey Weber and Iulia Giuroiu
  • Introduction
  • Interferon-α
  • Interleukin-2
  • Talimogene Laherparepvec
  • Granulocyte Macrophage Colony-Stimulating Factor
  • Tumor-Infiltrating Lymphocytes
  • Checkpoint Inhibitors—Cytotoxic T-Lymphocyte Antigen 4 and Programmed Cell Death Protein 1
  • Cytotoxic T-Lymphocyte Antigen 4 Blockade
  • Programmed Cell Death Protein 1 and Programmed Cell Death Protein Ligand 1 Blockade
  • Melanoma
  • Non–small-cell Lung Cancer
  • Mismatch-Repair Deficient or Microsatellite Instability-High Cancers
  • Renal Cell Carcinoma
  • Hodgkin Lymphoma
  • Head and Neck Squamous Cell Carcinoma
  • Urothelial Carcinoma
  • Merkel Cell Carcinoma
  • Hepatocellular Carcinoma
  • Gastric Cancer
  • Cervical Cancer
  • Primary Mediastinal Large B-Cell Lymphoma
  • Dosing
  • Vaccines
  • Sipuleucel-T
  • Conclusion
  • 9. Immunotherapy Agents
  • Jeffrey A. Sosman and Douglas B. Johnson
  • Introduction
  • Human Tumor Antigens
  • Mutanome-Associated Neoantigens
  • Tumor Vaccines
  • Personalized Neoantigen Vaccination
  • Immune Checkpoint Inhibitors
  • Other Immune Checkpoint Inhibitors in Development
  • Anti-TIGIT
  • TIM-3
  • LAG-3
  • KIR
  • CD73
  • VISTA
  • B7-H3
  • Immune Checkpoint Activators
  • 4-1BB (CD137)
  • GITR
  • ICOS
  • CD40
  • CD27-CD70
  • OX40
  • Oncolytic Viruses
  • Talimogene Laherparepvec
  • Other Oncolytic Viruses
  • Factors to Activate Immune Effector Cells
  • Cytokines
  • IL-2 Variant Molecules
  • Signaling Modulation
  • STAT3 Inhibition
  • PI3Kδ Inhibitors
  • PI3Kγ Inhibitors
  • Chemokine Inhibitors
  • CXCR2 Inhibitors
  • CCR2 Inhibitors
  • CXCR4 Inhibitors
  • CCR4 Antibodies
  • CCR5 Inhibitors
  • Soluble Factors
  • IDO Inhibition
  • Arginase Inhibitor
  • TGF-β Kinase Inhibitors
  • Adenosine A2α Receptor Axis
  • Adenosine Receptor Inhibitors
  • Innate Immune Modulation
  • Pathogen-Associated Molecular Patterns, Damage-Associated Molecular Patterns, and Pattern Recognition Receptors
  • Toll-Like Receptor Modulators
  • STING Agonists
  • Anti-CD47 Monoclonal Antibodies
  • Colony-Stimulating Factor 1 Receptor Inhibition
  • Bifunctional Fusion Proteins
  • Immunocytokines
  • Adoptive Cell Therapy
  • Chimeric Antigen Receptor T-Cell Therapy
  • 10. Monoclonal Antibodies
  • Hossein Borghaei, Matthew K. Robinson, Gregory P. Adams, and Louis M. Weiner
  • Introduction
  • Immunoglobulin Structure
  • Structural and Functional Domains
  • Modified Antibody-Based Molecules
  • Factors Regulating Antibody-Based Tumor Targeting
  • Antibody Size
  • Tumor Antigens
  • Half-Life/Clearance Rate
  • Glycosylation
  • Unconjugated Antibodies
  • Cell-Mediated Cytotoxicity
  • Complement-Dependent Cytotoxicity
  • Altering Signal Transduction
  • Immunoconjugates
  • Antibody–Drug Conjugates
  • Radioimmunoconjugates
  • Antibodies Approved for Use in Solid Tumors
  • Trastuzumab
  • Pertuzumab
  • Cetuximab
  • Panitumumab
  • Necitumumab
  • Bevacizumab
  • Ado-Trastuzumab Emtansine
  • Ramucirumab
  • Denosumab
  • Antibodies Used in Hematologic Malignancies
  • Rituximab
  • ofatumumab
  • Alemtuzumab
  • Brentuximab Vedotin
  • Inotuzumab Ozogamicin
  • Obinutuzumab
  • Blinatumomab
  • Daratumumab
  • Elotuzumab
  • Dinutuximab
  • Olaratumab
  • Conclusion
  • 11. Cancer Susceptibility Syndromes
  • Alice Hawley Berger and Pier Paolo Pandolfi
  • Introduction
  • Principles of Cancer Susceptibility
  • The “Two-Hit” Paradigm
  • What Is the Function of a Tumor Suppressor?
  • Haploinsufficiency and Compound Haploinsufficiency
  • Genetic Testing
  • Cancer Susceptibility Syndromes
  • Retinoblastoma
  • Incidence
  • Genetic Basis
  • Molecular Mechanism
  • Mouse Models
  • Clinical Features and Therapeutic Intervention
  • Most Prevalent Syndromes
  • Lynch Syndrome
  • Hereditary Breast and Ovarian Cancer
  • Neurofibromatosis Type 1
  • Familial Adenomatous Polyposis
  • Other Syndromes, by Function
  • Genomic Integrity and Apoptosis
  • Regulation of Protein Translation
  • Proliferation
  • Angiogenesis
  • Principles of Cancer Chemoprevention
  • Emerging Knowledge and New Lessons
  • Germline Mutations in Sporadic Cancer
  • Weak Modifiers
  • Epigenetic Factors
  • Role of Noncoding RNAs
  • The Regulatory Genome
  • High-Throughput Methods for Understanding Cancer Variants
  • Conclusion
  • 12. Pharmacogenomics
  • Christine M. Walko and Howard L. McLeod
  • Introduction
  • Pharmacogenomics of Tumor Response
  • Pathway-Directed Anticancer Therapy
  • Genetic-Guided Therapy: Practical Issues in Somatic Analysis
  • Pharmacogenomics of Chemotherapy Drug Toxicity
  • Thiopurine Methyltransferase
  • Dihydropyrimidine Dehydrogenase
  • Conclusions and Future Directions
  • 13. Genetic Counseling
  • Danielle C. Bonadies, Meagan B. Farmer, and Ellen T. Matloff
  • Introduction
  • Who is a Candidate for Cancer Genetic Counseling?
  • Components of the Cancer Genetic Counseling Session
  • Precounseling Information
  • Family History
  • Dysmorphology Screening
  • Risk Assessment
  • Genetic Testing
  • Options for Surveillance, Risk Reduction, and Tailored Treatment
  • Follow-up
  • Issues in Cancer Genetic Counseling
  • Genetic Test Selection and Approaches
  • Management of the Patient with a Pathogenic Variant in a Moderate-Risk or Lesser Known Gene
  • Genetic Testing in Children
  • Reproductive Issues
  • Potential Germline Implications of Tumor Genomic Profiling
  • Changes in Delivery Models
  • Direct-to-Consumer Genetic Testing
  • Psychosocial Issues
  • Confidentiality
  • Insurance and Discrimination Issues
  • Future Directions
  • Whole-Genome Sequencing and Whole-Exome Sequencing
  • General Population Testing
  • CRISPR
  • Conclusion
  • PART II: Molecular Biology of Individual Cancers
  • 14. The Molecular Biology of Head and Neck Cancers
  • Thomas E. Carey, Mark E. Prince, and J. Chad Brenner
  • Incidence, Risk Factors, and Etiology
  • Oral Tongue Cancer in Young Patients
  • High-Risk Hpv in Oropharyngeal Cancer
  • Molecular Mechanisms in Hnscc
  • The Cancer Genome Atlas Project
  • Inhibition of Hnscc Immune Escape
  • Cancer Stem Cells
  • 15. The Molecular Biology of Lung Cancer
  • Jill E. Larsen and John D. Minna
  • Introduction
  • Genomics: Tools for Identification, Prediction, and Prognosis
  • Somatic Landscape of Lung Cancer
  • Characterization of Aberrant Pathways
  • Transcriptome Profiling
  • Proteomic Approaches
  • Lessons Learned and Future Directions
  • Functional Genomics in Lung Cancer
  • Genome-wide RNA-Based and shRNA-Based Screening
  • CRISPR-Cas9 Gene Editing
  • Preclinical Model Systems for Studying Lung Cancer
  • Genetic and Epigenetic Alterations in Lung Cancer
  • EGFR/HER2/MET Signaling
  • EGFR
  • ERBB2 (HER2)
  • MET
  • RAS/RAF/MAPK Pathway
  • RAS
  • RAF
  • MEK (MAP2K1 or MEK1)
  • MYC
  • Pl3K/AKT/mTOR Pathway
  • STK11 (LKB1)
  • Insulin Growth Factor Pathway
  • Fibroblast Growth Factor Pathway
  • The p53 Pathway
  • The p16INK4a-RB Pathway
  • Fusion Proteins
  • ALK
  • ROS1
  • RET
  • NTRK
  • BRAF
  • EGFR
  • Epigenetic Changes in Lung Carcinogenesis
  • Methylation and Chromatin Remodeling
  • Noncoding RNAs
  • NFIB, a Metastasis-Inducing Transcription Factor
  • KDM Lysine Demethylases (JumonjiC) as an Epigenomic Drug Resistance Mechanism
  • Metastasis and the Tumor Microenvironment
  • Epithelial-to-Mesenchymal Transition
  • Angiogenesis
  • Immune Checkpoint Inhibition
  • Exosomes as a Source of Information on Tumor Molecular Alterations
  • Lung Cancers Stem Cells
  • Telomerase-Mediated Cellular Immortality in Lung Cancer
  • Clinical Translation of Molecular Data
  • Current Translation of Rationale-based Targeted Therapy
  • Potential for Future Clinical Translation
  • 16. Molecular Biology of the Esophagus and Stomach
  • Anil K. Rustgi
  • Introduction
  • Molecular Biology of Esophageal Cancer
  • Epidermal Growth Factor Receptor
  • Cyclin D1 and p16INK4a
  • TP53 Tumor Suppressor Genes
  • Telomerase Activation
  • Tumor Invasion and Metastasis
  • Models of Esophageal Squamous Cell Cancer and Esophageal Adenocarcinoma
  • Functional Genomics
  • Molecular Biology of Gastric Cancer
  • Inherited Susceptibility
  • Role of Helicobacter pylori Infection and Other Host–Environmental Factors
  • Molecular Genetic Alterations
  • Models of Gastric Cancer
  • 17. The Molecular Biology of Pancreas Cancer
  • Scott E. Kern and Ralph H. Hruban
  • Introduction
  • Common Genetic Changes in Pancreatic Ductal Adenocarcinoma
  • Less-Prevalent Genetic Changes in Pancreatic Ductal Adenocarcinoma
  • Other Neoplastic Lesions
  • 18. Molecular Biology of Liver Cancer
  • Jens U. Marquardt and Snorri S. Thorgeirsson
  • Introduction
  • Genetic Alterations in Liver Cancer
  • Epigenetic Alterations in Liver Cancer
  • Mutational Landscape of Genetic Alterations—The Next Generation
  • The Microenvironment of Liver Cancer
  • Classification and Prognostic Prediction of Hepatocellular Carcinoma
  • Molecular Basis of Cholangiocarcinoma
  • Conclusion and Perspective
  • 19. Molecular Biology of Colorectal Cancer
  • Ramesh A. Shivdasani
  • Introduction
  • Multistep Models of Colorectal Cancer and Genetic Instability
  • Mutational and Epigenetic Landscapes in Colorectal Cancer
  • Insights from Mouse Intestinal Crypts and Human Colorectal Cancers Lead to a Coherent Model for Colorectal Cancer Initiation and Progression
  • WNT Signaling
  • Other Growth Factor Pathways
  • Inherited Syndromes of Increased Cancer Risk Highlight Early Events and Critical Pathways in Colorectal Tumorigenesis
  • Familial Adenomatous Polyposis and the Central Importance of WNT Signaling
  • Hereditary Nonpolyposis Colorectal Cancer and the Role of DNA Mismatch Repair
  • Other Inherited Syndromes with Elevated Colorectal Cancer Risk
  • Familial Juvenile Polyposis
  • Insights from Mendelian Syndromes, Genome-Wide Association Studies, and the Microbiome
  • Oncogene and Tumor Suppressor Gene Mutations in Colorectal Cancer Progression
  • The KRAS, BRAF, and PIK3CA Oncogenes
  • MYC, CDK8, and Control of Cell Growth and Metabolism
  • TP53 and Other Tumor Suppressors
  • Prognostic and Predictive Value of Tumor Genotypes and Molecular Properties
  • 20. Molecular Biology of Kidney Cancer
  • W. Marston Linehan and Laura S. Schmidt
  • Introduction
  • Clear Cell Renal Cell Carcinoma
  • von Hippel-Lindau Disease
  • Genetics of von Hippel-Lindau Disease: VHL Gene
  • Gene Mutated in Renal Cancer Families with Chromosome 3p Translocations
  • Sporadic Clear Cell Kidney Cancer: VHL Gene Mutation
  • Function of the von Hippel-Lindau Protein
  • Additional Genes Mutated in Clear Cell Kidney Cancer
  • Papillary Renal Cell Carcinoma
  • Hereditary Papillary Renal Carcinoma: Type 1 Papillary
  • Genetics of Hereditary Papillary Renal Carcinoma: MET Protooncogene
  • Hereditary Papillary Renal Carcinoma: Functional Consequences of MET Mutations
  • Sporadic Type 1 Papillary Renal Cell Carcinoma
  • Xp11.2 Translocation Renal Cell Cancer
  • Hereditary Leiomyomatosis and Renal Cell Carcinoma: Type 2 Papillary
  • Hereditary Leiomyomatosis and Renal Cell Carcinoma: Fumarate Hydratase Gene
  • Functional Consequences of Fumarate Hydratase Mutations
  • Sporadic Type 2 Papillary Renal Cell Carcinoma
  • Chromophobe Renal Cell Carcinoma
  • Birt-Hogg-Dubé Syndrome
  • Birt-Hogg-Dubé Syndrome: FLCN Gene
  • Function of the Birt-Hogg-Dubé Protein: Folliculin
  • Sporadic Chromophobe Renal Cell Carcinoma
  • Additional Types of Renal Cell Carcinoma
  • Tuberous Sclerosis Complex
  • Succinate Dehydrogenase–Associated Renal Cancer
  • Conclusion
  • 21. Molecular Biology of Bladder Cancer
  • Carolyn D. Hurst and Margaret A. Knowles
  • Introduction
  • Mutational Landscape
  • Mutation Rates, Mutational Signatures, and Mutational Processes
  • FGFR3, PIK3CA, and RAS Genes
  • Telomerase Reverse Transcriptase Promoter
  • TP53, RB1, and CDKN2A
  • Genes Involved in Chromatin Modification and Architecture
  • STAG2
  • Alterations in DNA Repair Pathways
  • Structural Alterations to the Genome
  • Heterogeneity and Clonal Evolution
  • Molecular Subtypes
  • DNA-Based Subtypes
  • Transcriptome-Based Subtypes
  • Therapeutic Opportunities and Future Outlook
  • 22. The Molecular Biology of Prostate Cancer
  • Charles Dai and Nima Sharifi
  • Introduction
  • The Genomic Landscape of Prostate Cancer
  • The Molecular Subtypes of Primary Prostate Cancer
  • ETS Family Gene Fusions
  • Speckle-Type POZ Protein Mutations
  • Forkhead Box A1 Mutations
  • Serine Peptidase Inhibitor, Kazal Type 1 Overexpression
  • Isocitrate Dehydrogenase 1 Mutations
  • The Clonal Evolution of Lethal Metastatic Prostate Cancer
  • Genetic Basis of Prostate Cancer Heritability
  • Androgen Signaling in Prostate Cancer
  • androgen Receptor Structure and Function
  • androgen Receptor Action
  • Intratumoral androgen Biosynthesis
  • Glucocorticoid Signaling in Treatment Resistance
  • Other Signaling Pathways in Prostate Cancer
  • Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Pathway
  • Other Signaling Pathways in Prostate Cancer
  • Cell Cycle Aberrations
  • Neuroendocrine Prostate Cancer
  • Areas of Ongoing Research and Emerging Therapeutic Approaches
  • DNA Repair Pathway
  • Epigenetic Alterations
  • Conclusion
  • 23. Molecular Biology of Gynecologic Cancers
  • Tanja Pejovic, Adam J. Krieg, and Kunle Odunsi
  • Introduction
  • Ovarian Cancer
  • Origins of Epithelial Ovarian Cancer
  • Molecular Pathways to Ovarian Cancer
  • Inherited Syndromes of Ovarian Cancers
  • Targeting Homologous Recombination Defects in Gynecologic Cancer
  • Ovarian Cancer Microenvironment, Metastases, and Angiogenesis
  • Ovarian Cancer Microenvironment
  • Angiogenesis and Tumor Hypoxia
  • Influences of the Microenvironment on Tumor Metastasis
  • Epigenetics
  • Role of Specific Immune Responses and Immunotherapy
  • Immune Inhibitory Network and Immune Checkpoint Inhibitors in Ovarian Cancer
  • Immunotherapy Clinical Trials in Ovarian Cancer
  • Adoptive Cellular Transfer Therapy
  • Endometrial Cancer
  • Type I Cancers
  • Type II Endometrial Cancer
  • Microsatellite Instability
  • PTEN
  • KRAS Mutations
  • β-Catenin
  • Cervix, Vaginal, and Vulvar Cancers
  • Role of Human Papillomavirus
  • Immune Evasion by Human Papillomavirus
  • Human Papillomavirus Vaccines
  • Adoptive T-Cell Therapy
  • 24. Molecular Biology of Breast Cancer
  • Ana T. Nunes, Tara Berman, and Lyndsay Harris
  • Introduction
  • Genetics of Breast Cancer
  • Hereditary Breast Cancer
  • High-Penetrance, Low-Frequency Genes
  • Moderate-Penetrance, Low-Frequency Genes
  • Low-Penetrance, High-Frequency Genes and Loci
  • Microsatellite Instability in Breast Cancer
  • Somatic Alterations in Breast Cancer
  • Copy Number Alterations in Breast Cancer
  • Transcriptional Profiles of Breast Cancer—Molecular Subtypes
  • Luminal Subtypes
  • HER2-Enriched Subtype
  • Triple-Negative Subtypes
  • Mutational Profiles in Breast Cancer by Molecular Subtype
  • Transcriptional Profiles of Breast Cancer—Prognosis and Benefit of Therapy
  • 70-Gene Assay (Mammaprint)
  • 21-Gene Recurrence Score (Oncotype DX)
  • Prediction Analysis of Microarray-50 (PAM50, PAM50 Risk of Recurrence Score, or Prosigna)
  • 12-Gene Risk Score (Endopredict)
  • Two-Gene Ratio (Breast Cancer Index)
  • Epigenetics of Breast Cancer
  • Protein/Pathway Alterations
  • Estrogen Receptor Pathway
  • Growth Factor Receptor Pathways
  • Human Epidermal Growth Factor Receptor 2
  • RAS and Phosphatidylinositol 3-Kinase Signaling Pathways
  • Cyclin-Dependent Kinases
  • 25. Molecular Biology of Endocrine Tumors
  • Zeyad T. Sahli, Brittany A. Avin, and Martha A. Zeiger
  • Endocrine Syndromes
  • Multiple Endocrine Neoplasia Type 1
  • Clinical Features
  • Molecular Genetics of MEN1
  • Multiple Endocrine Neoplasia Type 2
  • Clinical Features of MEN2A
  • Clinical Features of MEN2B
  • Molecular Genetics of MEN2
  • Multiple Endocrine Neoplasia Type 4
  • Carney Complex
  • Clinical Features
  • Molecular Genetics of Carney Complex
  • Adrenal Gland
  • Cortisol-Producing Adenomas
  • Aldosterone-Producing Adenomas
  • Pheochromocytoma
  • Adrenocortical Carcinoma
  • Parathyroid Gland
  • Hyperparathyroidism–Jaw Tumor Syndrome
  • Familial Hypocalciuric Hypercalcemia
  • Neonatal Severe Hyperparathyroidism
  • Autosomal Dominant Hypoparathyroidism
  • Familial Isolated Hyperparathyroidism
  • Pituitary Gland
  • Familial Isolated Pituitary Adenoma
  • X-linked Acrogigantism
  • McCune-Albright Syndrome
  • Paraganglioma, Pheochromocytoma, and Pituitary Adenoma Association
  • Dicer1 Syndrome
  • Thyroid Gland
  • Follicular Adenomas
  • Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features
  • Papillary Thyroid Cancer
  • Follicular Thyroid Cancer
  • Hürthle Cell Carcinoma
  • Medullary Thyroid Cancer
  • Anaplastic Thyroid Cancer
  • Werner Syndrome
  • Acknowledgments
  • 26. Molecular Biology of Sarcomas
  • Samuel Singer and Cristina R. Antonescu
  • Introduction
  • Soft Tissue Sarcomas
  • Translocation-Associated Soft Tissue Sarcomas
  • Myxoid/Round Cell Liposarcoma
  • Ewing Sarcoma
  • Desmoplastic Small Round Cell Tumor
  • Synovial Sarcoma
  • Alveolar Rhabdomyosarcoma
  • Alveolar Soft Part Sarcoma
  • Dermatofibrosarcoma Protuberans
  • Extraskeletal Myxoid Chondrosarcoma
  • Solitary Fibrous Tumor and Hemangiopericytoma
  • Soft Tissue Sarcomas of Simple Karyotype Associated With Mutations
  • Desmoid Fibromatosis
  • Complex Soft Tissue Sarcoma Types
  • Well-Differentiated and Dedifferentiated Liposarcoma
  • Pleomorphic Liposarcoma
  • Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma (Malignant Fibrous Histiocytoma)
  • Myxofibrosarcoma
  • Undifferentiated Pleomorphic Sarcoma (Malignant Fibrous Histiocytoma)
  • Leiomyosarcoma
  • Malignant Peripheral Nerve Sheath Tumor
  • Angiosarcoma
  • Bone and Cartilaginous Tumors
  • Cartilaginous Tumors
  • Enchondroma
  • Osteochondroma
  • Chondrosarcoma
  • Osteosarcoma
  • Future Directions: Next-Generation Sequencing and Functional Screens
  • 27. Molecular Biology of Cutaneous Melanoma
  • Michael A. Davies
  • Introduction
  • The Cancer Genome Atlas Effort in Cutaneous Melanoma
  • The Ras-Raf-Mapk Pathway
  • RAF Kinases
  • RAS Family GTPases
  • NF1
  • Additional Oncogenic Pathways
  • Cell Cycle Regulators
  • The p53 Pathway
  • The Phosphatidylinositol 3-Kinase Pathway
  • Receptor Tyrosine Kinases
  • RAC1
  • Telomerase
  • Triple Wild-Type Melanomas
  • Melanin Synthesis Pathway
  • MITF
  • The MC1R Pathway
  • Summary and Future Directions
  • 28. Molecular Biology of Central Nervous System Tumors
  • Mark W. Youngblood, Jennifer Moliterno Günel, and Murat Günel
  • Introduction
  • Pediatric Brain Tumors
  • Medulloblastoma
  • Low-Grade Glioma
  • High-Grade Glioma
  • Ependymal Tumors
  • Adult Brain Tumors
  • Low-Grade Glioma
  • High-Grade Glioma
  • Meningioma
  • Summary
  • Acknowledgments
  • 29. Molecular Biology of Lymphoma
  • Nicolò Compagno, Laura Pasqualucci, and Riccardo Dalla-Favera
  • Introduction
  • The Cell of Origin of Lymphoma
  • B-Cell Development and the Dynamics of the Germinal Center Reaction
  • T-Cell Development
  • General Mechanisms of Genetic Alterations in Lymphoma
  • Chromosomal Translocations
  • Aberrant Somatic Hypermutation
  • Copy Number Gains and Amplifications
  • Activating Point Mutations
  • Inactivating Mutations and Deletions
  • Infectious Agents
  • Molecular Pathogenesis of B-Cell Non-Hodgkin Lymphoma
  • Mantle Cell Lymphoma
  • Cell of Origin
  • Genetic Lesions
  • Burkitt Lymphoma
  • Cell of Origin
  • Genetic Lesions
  • Follicular Lymphoma
  • Cell of Origin
  • Genetic Lesions
  • Diffuse Large B-Cell Lymphoma
  • Cell of Origin
  • Genetic Lesions
  • Primary Mediastinal B-Cell Lymphoma
  • Cell of Origin
  • Genetic Lesions
  • Marginal Zone Lymphoma
  • Cell of Origin
  • Genetic Lesions
  • Chronic Lymphocytic Leukemia
  • Cell of Origin
  • Genetic Lesions
  • Molecular Pathogenesis of T-Cell Non-Hodgkin Lymphoma
  • Adult T-Cell Leukemia/Lymphoma (HTLV-1 Positive)
  • Cell of Origin
  • Genetic Lesions
  • Angioimmunoblastic T-Cell Lymphoma
  • Cell of Origin
  • Genetic Lesions
  • Peripheral T-Cell Lymphoma Not Otherwise Specified
  • Genetic Lesions
  • Cutaneous T-Cell Lymphoma
  • Anaplastic Large-Cell Lymphoma
  • Cell of Origin
  • Genetic Lesions
  • Hepatosplenic T-Cell Lymphoma
  • Molecular Pathogenesis of Hodgkin Lymphoma
  • Cell of Origin
  • Genetic Lesions
  • 30. Molecular Biology of Acute Leukemias
  • Glen D. Raffel and Jan Cerny
  • Introduction
  • Leukemic Stem Cell
  • Elucidation of Genetic Events in Acute Leukemia
  • Mutations Affecting Transcription Factors
  • Core-Binding Factor
  • Retinoic Acid Receptor Alpha Gene
  • HOX Family Members
  • C/EBPα
  • GATA Factors
  • Mutations that Result in Overexpression of c-MYC
  • Mutation of Lymphoid Development Factors in Acute Lymphoid Leukemia
  • Chromosomal Translocations Involving the T-cell Receptor
  • RBM15/MKL1
  • Mutations of Epigenetic Modifiers
  • KMT2A (aka MLL) Translocations
  • MOZ and TIF2
  • TET2
  • DNMT3A
  • ASXL1
  • EZH2
  • Mutations Affecting Signaling
  • Oncogenic RAS Mutations
  • Activating Mutations in Tyrosine Kinases and Associated Receptors
  • BCR/ABL1
  • FLT3
  • KIT
  • MPL
  • JAK/STAT Pathway
  • CRLF2
  • Kinases in Ph-Negative Acute Lymphoid Leukemia
  • Mutations in Tumor Suppressor Genes
  • WT1
  • TP53
  • Activating Mutations of Notch
  • Mutations Altering Localization of Npm1
  • Mutations in Cohesin Complex Genes
  • Mutations in Splicing Machinery
  • Mutational Complementation Groups in Acute Leukemias
  • Conclusion
  • 31. Molecular Biology of Chronic Leukemias
  • Christopher A. Eide, James S. Blachly, and Anupriya Agarwal
  • Introduction
  • Chronic Myeloid Leukemia
  • Pathogenesis
  • Molecular Anatomy of the BCR-ABL1 Junction
  • Functional Domains of BCR-ABL1 and Kinase Activation
  • Signal Transduction
  • Phosphatidylinositol-3 Kinase
  • Rat Sarcoma/Mitogen-Activated Protein Kinase Pathways
  • Janus Kinase/Signal Transducer and Activator of Transcription Pathway
  • DNA Repair
  • Chronic Myeloid Leukemia Stem Cells
  • Progression to Blastic Phase
  • Chronic Myeloid Leukemia Bone Marrow Microenvironment
  • Conclusions
  • Chronic Lymphocytic Leukemia
  • Origin of Chronic Lymphocytic Leukemia
  • Chromosomal Abnormalities in the Pathogenesis of Chronic Lymphocytic Leukemia
  • Recurrent Mutations in Chronic Lymphocytic Leukemia
  • Progression of Chronic Lymphocytic Leukemia: The Role of Genomic Instability and Clonal Evolution
  • Chronic Lymphocytic Leukemia and Proliferation
  • Chronic Lymphocytic Leukemia and Disrupted Apoptosis
  • B-cell Receptor Signaling in Chronic Lymphocytic Leukemia
  • Conclusion
  • Acknowledgments
  • Index