Molecular Pathology

The Molecular Basis of Human Disease

Edited by

  • William Coleman, Professor, Department of Pathology and Laboratory Medicine, UNC Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA
  • Gregory Tsongalis, Professor of Pathology, Director, Molecular Pathology, and Co-Director Translational Research Program, Department of Pathology, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA

Molecular Pathology: The Molecular Basis of Human Disease provides a current and comprehensive view of the molecular basis and mechanisms of human disease. Combining accepted principles with broader theoretical concepts and with contributions from a group of experts, the book looks into disease processes in the context of traditional pathology and their implications for translational molecular medicine. It also discusses concepts in molecular biology and genetics, recent scientific and technological advances in modern pathology, the concept of ""molecular pathogenesis"" of disease, and how disease evolves from normal cells and tissues due to perturbations in molecular pathways. The book describes the integration of molecular and cellular pathogenesis using a bioinformatics approach and a systems biology approach to disease pathogenesis. It also discusses current and future strategies in molecular diagnosis of human disease, and the impact of molecular diagnosis on treatment decisions and the practice of personalized medicine. This book is a valuable resource for students, biomedical researchers, practicing physician-scientists who undertake disease-related basic science and translational research, and pathology residents and other postdoctoral fellows.
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Medical students, pathology graduate students, biomedical graduate students, and some allied health students.


Book information

  • Published: February 2009
  • ISBN: 978-0-12-374419-7


"The editors of Molecular Pathology have produced a comprehensive compendium of the state-of-the-art in molecular pathogenesis, an impressive accomplishment given the diverse cells and organ systems involved in human disease. An established cadre of experts has contributed to this first, well-designed edition. As a result, essential topics ranging from cell injury/death, the molecular basis of cardiovascular diseases and disorders of the nervous system, and modern molecular diagnostics are amply addressed. In a rapidly emerging discipline, it is challenging to capture the details that define the field. Molecular Pathology has accomplished this goal in an outstanding manner and will serve as an excellent resource for those already established in clinical care and biomedical research, for those who seek to maintain competency in molecular pathology, as well as for all students involved in interdisciplinary studies related to human disease or modern clinical investigations."

--Linda M. McManus, PhD, Professor, University of Texas Health Science Center at San Antonio

"The focus of Molecular Pathology is genetic and molecular but it has been written to enhance the work of an active pathologist, clearly describing the basics as well as providing ample sampling of the molecular complexities of disease. Gladly the editors did not assemble an exhaustive compendium of facts and details that would inevitably become obsolete in short order. Instead, the contributors concentrated on clarity of explanation supported by selected examples so that the reader may grasp the fundamentals better. In fact, this may be one medical textbook that can be read cover-to-cover without being lost in details. The figures are clear, helpful, and plentiful which is important when dealing with so many complex technologies and concepts. I highly recommend this book."

--Edison T. Liu, M.D, Executive Director, Genome Institute of Singapore

Table of Contents

List of Contributors




Part I Essential Pathology - Mechanisms of Disease

    Chapter 1 Molecular Mechanisms of Cell Death


         Modes of Cell Death

         Structural Features of Necrosis and Apoptosis

         Cellular and Molecular Mechanisms Underlying Necrotic Cell Death

         Pathways to Apoptosis



         Endoplasmic Reticulum


         Concluding Remark

    Chapter 2 Acute and Chronic Inflammation Induces Disease Pathogenesis


         Leukocyte Adhesion, Migration, and Activation

         Acute Inflammation and Disease Pathogenesis

         Pattern Recognition Receptors and Inflammatory Responses

         Chronic Inflammation and Acquired Immune Responses

         Tissue Remodeling During Acute and Chronic Inflammatory Disease

    Chapter 3 Infection and Host Response

         Microbes and Hosts-Balance of Power?

         The Structure of the Immune Response

         Regulation of Immunity

         Pathogen Strategies

         The African Trypanosome and Antibody Diversity: Dueling Genomes

         Staphylococcus Aureus: the Extracellular Battleground

         Mycobacterium Tuberculosis and the Macrophage

         Herpes Simplex Virus: Taking Over

         HIV: The Immune Guerilla


    Chapter 4 Neoplasia


         Cancer Statistics and Epidemiology

         Classification of Neoplastic Diseases

         Characteristics of Benign and Malignant Neoplasms

         Clinical Aspects of Neoplasia

Part II Concepts in Molecular Biology and Genetics

    Chapter 5 Basic Concepts in Human Molecular Genetics


         Molecular Structure of DNA, DNA Transcription, and Protein Translation

         Molecular Pathology and DNA Repair Mechanisms

         Modes of Inheritance

         Central Dogma and Rationale for Genetic Testing

         Allelic Heterogeneity and Choice of Analytical Methodology


    Chapter 6 The Human Genome: Implications for the Understanding of Human Disease


         Structure and Organization of the Human Genome

         Overview of the Human Genome Project

         Impact of the Human Genome Project on the Identification of Disease-Related Genes

         Sources of Variation in the Human Genome

         Types of Genetic Diseases

         Genetic Diseases and Cancer


    Chapter 7 The Human Transcriptome: Implications for the Understanding of Human Disease


         Gene Expression Profiling: The Search for Candidate

         Genes Involved in Pathogenesis

         Transcriptome Analysis Based on Microarrays: Technical Prerequisites

         Microarrays: Bioinformatic Analysis

         Microarrays: Applications in Basic Research and Translational Medicine Perspectives

    Chapter 8 The Human Epigenome: Implications for the Understanding of Human Disease


         Epigenetic Regulation of the Genome

         Genomic Imprinting

         Cancer Epigenetics

         Human Disorders Associated with Epigenetics

         Environment and the Epigenome

    Chapter 9 Clinical Proteomics and Molecular Pathology

         Understanding Cancer at the Molecular Level: An Evolving Frontier

         Microdissection Technology Brings Molecular Analysis to the Tissue Level

         Serum Proteomics: An Emerging Landscape for Early Stage Cancer Detection

    Chapter 10 Integrative Systems Biology: Implications for the Understanding of Human Disease


         Data Generation

         Data Integration

         Modeling Systems

         Implications for Understanding Disease


Part III Principles and Practice of Molecular Pathology

    Chapter 11 Pathology: The Clinical Description of Human Disease


         Terms, Definitions, and Concepts

         A Brief History of Approaches to Disease

         Current Practice of Pathology

         The Future of Diagnostic Pathology


    Chapter 12 Understanding Molecular Pathogenesis: The Biological Basis of Human Disease and Implications for Improved Treatment of Human Disease


         Hepatitis C Virus Infection

         Acute Myeloid Leukemia

         Cystic Fibrosis

    Chapter 13 Integration of Molecular and Cellular Pathogenesis: A Bioinformatics



         Overview of Bioinformatics

         Database Resources

         Data Analysis

         The Future of Bioinformatics

    Chapter 14 Molecular Basis of Cardiovascular Disease


         General Molecular Principles of Cardiovascular


         The Cells of Cardiovascular Organs


         Ischemic Heart Disease



         Valvular Heart Disease


    Chapter 15 Molecular Basis of Hemostatic and Thrombotic Diseases

         Introduction and Overview of Coagulation

         Disorders of Soluble Clotting Factors

         Disorders of Fibrinolysis

         Disorders of Platelet Number or Function


    Chapter 16 Molecular Basis of Lymphoid and Myeloid Diseases

         Development of the Blood and Lymphoid Organs

         Myeloid Disorders

         Lymphocyte Disorders

    Chapter 17 Molecular Basis of Diseases of Immunity


         Normal Immune System

         Major Syndromes

    Chapter 18 Molecular Basis of Pulmonary Disease


         Neoplastic Lung and Pleural Diseases

         Non-neoplastic Lung Disease

         Obstructive Lung Diseases

         Interstitial Lung Diseases

         Pulmonary Vascular Diseases

         Pulmonary Infections

         Pulmonary Histiocytic Diseases

         Pulmonary Occupational Diseases

         Developmental Abnormalities

    Chapter 19 Molecular Basis of Diseases of the Gastrointestinal Tract


         Gastric Cancer

         Colorectal Cancer

    Chapter 20 Molecular Basis of Liver Disease


         Molecular Basis of Liver Development

         Molecular Basis of Liver Regeneration

         Adult Liver Stem Cells in Liver Health and Disease

         Molecular Basis of Hepatocyte Death

         Molecular Basis of Nonalcoholic Fatty Liver Disease

         Molecular Basis of Alcoholic Liver Disease

         Molecular Basis of Hepatic Fibrosis and Cirrhosis

         Molecular Basis of Hepatic Tumors

    Chapter 21 Molecular Basis of Diseases of the Exocrine Pancreas

         Acute Pancreatitis

         Chronic and Hereditary Pancreatitis


    Chapter 22 Molecular Basis of Diseases of the Endocrine System


         The Pituitary Gland

         The Thyroid Gland

         The Parathyroid Gland

         The Adrenal Gland


    Chapter 23 Molecular Basis of Gynecologic Diseases


         Benign and Malignant Tumors of the Female

         Reproductive Tract

         Disorders Related to Pregnancy

    Chapter 24 Molecular Pathogenesis of Prostate Cancer: Somatic, Epigenetic, and Genetic Alterations


         Hereditary Component of Prostate Cancer Risk

         Somatic Alterations in Gene Expression


         Advances in Mouse Models of Prostate Cancer



    Chapter 25 Molecular Biology of Breast Cancer


         Traditional Breast Cancer Classification


         Gene Expression Profiling


    Chapter 26 Molecular Basis of Skin Disease


         Skin Diseases and Their Impact

         Molecular Basis of Healthy Skin

         Skin Development and Maintenance Provide New Insight into the Molecular Mechanisms of Disease

         Molecular Pathology of Mendelian Genetic Skin Disorders

         Molecular Pathology of Common Inflammatory Skin Diseases

         Skin Proteins as Targets for Inherited and Acquired Disorders

         Molecular Pathology of Skin Cancer

         Molecular Diagnosis of Skin Disease

         New Molecular Mechanisms and Novel Therapies

    Chapter 27 Molecular Pathology: Neuropathology

         Anatomy of the Central Nervous System

         Neurodevelopmental Disorders

         Neurological Injury: Stroke, Neurodegeneration, and Toxicants


         Disorders of Myelin

Part V Practice of Molecular Medicine

    Chapter 28 Molecular Diagnosis of Human Disease


         History of Molecular Diagnostics

         Molecular Laboratory Subspecialties

         Future Applications

    Chapter 29 Molecular Assessment of Human Disease in the Clinical Laboratory


         The Current Molecular Infectious Disease Paradigm

         A New Paradigm for Molecular Diagnostic Applications

         BCR-ABL: A Model for the New Paradigm


    Chapter 30 Pharmacogenomics and Personalized Medicine in the Treatment of Human