Clinical Genomics: The Impact of Genomic Technology on Clinical Trials and Medical Practice

Table of Contents

Executive Summary

Chapter 1. Introduction

1.1. Genomics in the Clinic

-A Vision of the Future

-Definition of Clinical Genomics

-The Human Genome

1.2. Prec linical Versus Clinical Applications of Genomics

1.3. Impact of Human Genome Information

-The Human Genome Project

--Brief Timeline of Human Genomics

-Major Discoveries About the Human Genome

-NIH Forecast of the Impact of Genomics

--NHGRI Vision for the Future of Genomics

Chapter 2. Promises and Challenges of Clinical Genomics

2.1. The Promise of Clinical Genomics

-Advantages of a Genomics Approach

-Potential Impact on Medical Practice

-Potential Impact on Drug Development

2.2. Challenges in the Field

-Scientific Challenges

-Technological Challenges

-Regulatory Challenges

-Legal Challenges

-- The Biojudiciary Project

-Economic Challenges

-Sociological and Cultural Challenges

Commentary by Geoffrey Ginsburg, Millennium Pharmaceuticals

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Chapter 3. Clinical Genomics Applications:

Prediction, Detection, and Diagnosis

Genomic Characteristics with Clinical Applications

3.1. Determining Risk of Disease

-Inherited Genetic Variation

-Categories of Inherited DNA Diseases

-Single-Gene Genetic Disorders

-Multifactorial Disorders

--Genetic Origin of Cancers

3.2. Predicting Response to Drugs

-Pharmacogenomics

3.3. Factors Influencing Response to Drugs

-Drug Metabolism

-Drug Transporters

-Genetic Pol ymorphism of Drug Targets

-Genetic Variants with Indirect Effects on Drug Response

3.4. Diagnose and Monitor Diseases

-Variation in Gene Expression

-Cancer Classification, Diagnosis, and Prognosis

--Cancer Genome Anatomy Project

3.5. Detecting Response to the Environment

-Toxicogenomics

--National Center for Toxicogenomics

-Combating Bioterrorism

-Infectious Disease Susceptibility

3.6. Identifying Individuals: Paternity and Forensics Testing

-Paternity Testing

-Forensics

-Identifying Remains

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Chapter 4. Genomic Technologies for the Clinic

4.1. DNA Variation: Detection and Genotyping

-Single Nucleotide Polymorphisms (SNPs)

-Haplotype Map

--HapMap Project

-SNP Genotyping Methods

-Evaluating SNP Technologies for Clinical Applications

-Popular SNP Genotyping Technologies

--Selected Companies Providing SNP Technology, Services, or Reagents

-Techniques for Identity Testing

4.2. Gene Expression Detection

-Measuring Gene Expression

-DNA Microarrays

-Computational Issues

--Microarray Gene Expression Data (MGED) Society

-Laser Capture Microdissection

-Evaluating the Technologies

4.3. Other Technologies

-Molecular Imaging

-Gene Therapy

-Proteomics

Commentary by David Craford, Affymetrix

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Chapter 5. Current Applications of Clinical Genomics

5.1. Overview

-Preclinical Applications

5.2. Applications in Clinical Trials

-Early Phase Applications

-Banking Blood

Commentary by Todd R. Golub, Dana-Farber Cancer Institute

5.3. Applications of Gene Expression Analysis

-Oncology Clinical Trials

-Breast Cancer Gene Expression Analysis

-Future Clinical Medicine Applications of Gene Expression Assays

-Technical Limitations

-Preclinical Studies

5.4. Applications in Toxicogenomics

-Toxicogenomic Application Example #1: TPMT

-Toxicogenomic Application Example #2: CYP450s

-Future Prospects for Toxicogenomic Applications

5.5. App lications in Cancer

-Cancer Application Example #1: Her-2 and Herceptin

-Cancer Application Example #2: BRCA1 and BRCA2 Genes

5.6. Applications in Infectious Diseases

-Infectious Disease Application Example: HIV Resistance Testing

-Other HIV Applications

5.7. Applications in Cardiovascular Disease

-Cadiovascular Disease Application Example: Factor V Leiden

5.8. Other Applications

-Genomic Profiling

-Newborn Screening

-Prenatal Testing

-Identity Testing

-Paternity Testing

-Forensics Testing

Chapter 6. Business and Strategic Issues

6.1. Overview

6.2. Key Factors Driving Adoption

-Patients and Patient Groups

-Ma naged Care Providers

-Pharmaceutical Industry

-Government and Regulatory Authorities

-Improved Technologies

-Legal System

-Proof Applications

6.3. Cost Evaluation of Clinical Genomics

-Measuring Costs

-Factors Influencing Costs

-Comparing Costs to Other Treatment Options

-Cost-Benefit and Cost-Effectiveness Analysis

-Specific Evaluations

6.4. Regulatory Environment

-FDA Draft Guidelines on Pharmacogenomics

-"Home-Brew�h Testing

6.5. Clinical Genomics Diagnostics Market

6.6. Market Outlook

-Toxicogenomics

-Oncology

-Infectious Disease

-Inherited Disease

-Identity Screening

6.7. Business Opportunities

Commentary by David Wang, First Genetic Trust

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Appendix. Selected Clinical Genomics Companies

Abbott Diagnostics

ACLARA BioSciences

Agendia

Arcturus

Ardais

deCODE genetics

diaDexus

EXACT Sciences

ExonHit Therapeutics

First Genetic Trust

Genaissance Pharmaceuticals

Gene Logic

Genomic Health

Genomics Collaborative

Gentris Corporation

Iconix Pharmaceuticals, Inc.

Interleukin Genetics

LabCorp

Moltox (Molecular Toxicology Inc.)

Myriad Genetics, Inc.

ParAllele BioScience

Perlegen Sciences, Inc.

PointOne

Roche Molecular Diagnostics

SEQUENOM

Spectral Genomics, Inc.

SurroMed

Glossary

Index