Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page R1
Advances in Understanding Genetic Changes in Cancer: Impact on Diagnosis and Treatment Decisions in the 1990s ADVANCES IN UNDERSTANDING GENETIC CHANGES IN CANCER Impact on Diagnosis and Treatment Decisions in the 1990s A Research Briefing from the Division of Health Sciences Policy INSTITUTE OF MEDICINE National Academy Press Washington, D.C. 1992
OCR for page R2
Advances in Understanding Genetic Changes in Cancer: Impact on Diagnosis and Treatment Decisions in the 1990s The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy’s 1863 Congressional charter responsibility to be an advisor to the federal government, and its own initiative in identifying issues of medical care, research, and education. Research briefings are an important part of the agreement between the Institute of Medicine and the Howard Hughes Medical Institute to initiate a program of studies that is intended to facilitate the translation of discoveries in basic science into advances for health. Of specific interest in the research briefings are the assessment of current knowledge in a particular field of study, identification of promising areas within that field, and recommendations about future research needs in terms of scientific issues. Although occasional recommendations are made regarding research policy, it is not the purpose of these briefings to advocate increases or decreases in current funding levels or to undertake a prioritization or comparative evaluation of other areas of scientific inquiry. The audience for research briefings is quite broad and includes grant administrators and project officers (government and nongovernment), physicians, science policy analysts, congressional staff, scientists, science journalists, and the interested lay public. Research briefing topics are selected by the Institute of Medicine in consultation with its membership, the IOM Council, and the Board on Health Sciences Policy. Library of Congress Catalog Card No. 92-60001 International Standard Book Number 0-309-04688-2 Additional copies of this report are available from: National Academy Press 2101 Constitution Avenue, N.W. Washington, D.C. 20418 S537 Printed in the United States of America The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatlichemuseen in Berlin.
OCR for page R3
Advances in Understanding Genetic Changes in Cancer: Impact on Diagnosis and Treatment Decisions in the 1990s PANEL FOR THE RESEARCH BRIEFING ON ADVANCES IN UNDERSTANDING GENETIC CHANGES IN CANCER: IMPACT ON DIAGNOSIS AND TREATMENT DECISIONS IN THE 1990s JANET D. ROWLEY (Co-Chair), Department of Medicine and of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois JEFFREY L. SKLAR (Co-Chair), Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts GARRETT M. BRODEUR, Division of Hematology/Oncology, St. Louis Children's Hospital, St. Louis, Missouri WEBSTER K. CAVENEE, Ludwig Institute-Montreal Branch, Montreal, Quebec, Canada BEVERLY F. EMANUEL, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania STANLEY J. KORSMEYER, Howard Hughes Medical Institute, St. Louis, Missouri DANIEL PINKEL, Division of Molecular Cytometry, University of California at San Francisco, San Francisco, California DENNIS J. SLAMON, Division of Hematology/Oncology, University of California at Los Angeles, Los Angeles, California SANFORD A. STASS, Division of Laboratory Medicine, M.D. Anderson Cancer Center, Houston, Texas LOUIS C. STRONG, Division of Pediatrics, M.D. Anderson Cancer Center, Houston, Texas Rapporteur JON C. ASTER, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts Institute of Medicine Staff DAVID M. TURNER, Project Director, Research Briefing RUTH ELLEN BULGER, Director, Division of Health Sciences Policy SARAH A. ZIELINSKI, Project Assistant RITA T. GIBSON, Administrative Assistant
OCR for page R4
Advances in Understanding Genetic Changes in Cancer: Impact on Diagnosis and Treatment Decisions in the 1990s Statement of Purpose Committee for the Research Briefing on Advances in Understanding Genetic Changes in Cancer: Impact on Diagnosis and Treatment Decisions in the 1990s The purpose of this committee was to conduct a research briefing to examine the utilization of genetic techniques for the diagnosis and prognosis of cancer and the impact of this utilization on diagnosis, prognosis, and treatment decisions. Research briefings are sponsored by the Howard Hughes Medical Institute and address three purposes: (1) to highlight a promising and exciting field of medical science; (2) to examine the current status of that field; and (3) to make scientific recommendations about future needs in the field. This research briefing is directed largely toward informing physicians of the rapid advances being made in this field.
OCR for page R5
Advances in Understanding Genetic Changes in Cancer: Impact on Diagnosis and Treatment Decisions in the 1990s Contents 1 Introduction 1 Outline of Molecular Genetics 2 Brief Overview of Cancer Genetics 3 2 Testing for Tumor-Specific Genetic Markers 8 Microscopic Detection of Alterations in DNA Structure 9 In Situ Hybridization 12 Ploidy Analysis 15 Techniques for Detecting Changes in DNA Structure at the Submicroscopic Level 16 Southern Blot Hybridization 16 Pulsed-Field Gel Electrophoresis 18 Polymerase Chain Reaction 19 Techniques for Detection of Point Mutations in DNA 21 Techniques Directed at Analysis of RNA 22 Techniques for Analyzing Changes at the Protein Level 23 Immunohistochemistry 23 3 Hematologic Cancer 25 Chronic Myelogenous Leukemia 25 Chronic Lymphocytic Leukemia 32 Acute Lymphocytic Leukemia 32 Acute Myelogenous Leukemia 36 Myelodysplastic Syndromes 38 Lymphoma 39
OCR for page R6
Advances in Understanding Genetic Changes in Cancer: Impact on Diagnosis and Treatment Decisions in the 1990s 4 Solid Tumors 45 Chromosomal Aberrations of Diagnostic Importance 47 Chromosomal Aberrations of Prognostic Importance 48 Neuroblastoma 48 Breast Cancer 50 Lung Cancer 52 Other Solid Tumors 53 Genetic Markers of Predisposition to Cancer 53 Retinoblastoma 53 Mapping of Other Cancer Predisposition Loci 55 Li-Fraumeni Syndrome 57 Loss of Heterozygosity in Sporadic Solid Tumors 58 Genetic Changes and Tumor Progression 59 Colorectal Neoplasms 59 Glial Tumors 61 Cancer-Associated Genetic Changes and Environmental Mutagens 62 Viral Markers in Cancer Diagnosis 62 5 Summary and Specific Recommendations 65 Practical Aspects of Genetic Analysis: From Patient to Diagnostic Laboratory 66 The Molecular Diagnostic Laboratory 67 Implications of Commercialization 67 Future Needs 68 6 References 69
OCR for page R7
Advances in Understanding Genetic Changes in Cancer: Impact on Diagnosis and Treatment Decisions in the 1990s ADVANCES IN UNDERSTANDING GENETIC CHANGES IN CANCER
OCR for page R8
Advances in Understanding Genetic Changes in Cancer: Impact on Diagnosis and Treatment Decisions in the 1990s This page in the original is blank.