The Molecular Basis of Cancer

1019 Pages·2015·33.05 MB·English

by  John Mendelsohn

Edition 4
The Molecular
Basis of Cancer
John Mendelsohn, MD
Director, Khalifa Institute for Personalized Cancer Therapy
and Past President
The University of Texas M. D. Anderson Cancer Center
Houston, Texas
Joe W. Gray, PhD
Gordon Moore Endowed Chair
Chairman, Department of Biomedical Engineering
Director, OHSU Center for Spatial Systems Biomedicine
Associate Director for Translational Research
Knight Cancer Institute
Oregon Health and Science University (OHSU)
Portland, Oregon
Peter M. Howley, MD
Shattuck Professor of Pathological Anatomy
Department of Microbiology and Immunobiology
Division of Immunology
Harvard Medical School
Boston, Massachusetts
Mark A. Israel, MD
Director, Norris Cotton Cancer Center
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire
Professor of Pediatrics and Genetics
Geisel School of Medicine at Dartmouth
Hanover, New Hampshire
Craig B. Thompson, MD
President and CEO, Memorial Sloan-Kettering Cancer Center
New York, New York
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
THE MOLECULAR BASIS OF CANCER ISBN: 978-1-4557-4066-6
Copyright © 2015, 2008, 2001, 1995 by Saunders, an imprint of Elsevier Inc.
All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic
or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission
in writing from the Publisher. Details on how to seek permission, further information about the Publisher’s permissions
policies, and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing
Agency, can be found at our website: www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as
may be noted herein).
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden our under-
standing, changes in research methods, professional practices, or medical treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any
information, methods, compounds, or experiments described herein. In using such information or methods they
should be mindful of their own safety and the safety of others, including parties for whom they have a professional
responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the most current infor-
mation provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to ver-
ify the recommended dose or formula, the method and duration of administration, and contraindications. It is the
responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to
determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for
any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any
use or operation of any methods, products, instructions, or ideas contained in the material herein.
Library of Congress Cataloging-in-Publication Data
The molecular basis of cancer / [edited by] John Mendelsohn, Peter M. Howley, Mark A. Israel, Joe W. Gray, Craig B.
Thompson. -- 4.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4557-4066-6 (hardcover : alk. paper)
I. Mendelsohn, John, 1936- editor of compilation. II. Howley, Peter M., editor of compilation. III. Israel, Mark A.,
editor of compilation. IV. Gray, Joe W., editor of compilation. V. Thompson, Craig (Craig B.), editor of compilation.
[DNLM: 1. Neoplasms--genetics. 2. Neoplasms--pathology. 3. Molecular Biology--methods. 4. Molecular Targeted
Therapy.  QZ 202]
RC268.5
616.99’4071--dc23 2013034109
Senior Content Strategist: Suzanne Toppy
Senior Content Development Specialist: Taylor Ball
Publishing Services Manager: Patricia Tannian
Senior Project Manager: Sharon Corell
Senior Book Designer: Louis Forgione
Printed in China
Last digit is the print number: 9 8 7 6 5 4 3 2 1
This book is dedicated to our wives:
Anne C. Mendelsohn
Jane E. Gray
Ann Howley
Susan J. Israel
Tullia Lindsten
Contributors
Stuart A. Aaronson, MD Jennifer Amengual, MD
Professor and Chair Assistant Professor of Medicine and Experimental
Department of Oncological Sciences Therapeutics
Professor of Medicine Center for Lymphoid Malignancies
Mount Sinai School of Medicine Department of Medicine
New York, New York Division of Hematopathology
Department of Pathology and Cell Biology
James L. Abbruzzese, MD Columbia University Medical Center–College of Physicians
Chief and Surgeons
Division of Medical Oncology The New York Presbyterian Hospital
Associate Director for Clinical Research New York, New York
Duke Cancer Institute
Kenneth C. Anderson, MD
Durham, North Carolina
Chief
Erika L. Abel, PhD Jerome Lipper Multiple Myeloma Center
Lecturer/Advisor of Biology Dana-Farber Cancer Institute
Department of Biology Boston, Massachusetts
College of Arts and Sciences
Olena Barbash, PhD
Baylor University
Investigator
Waco, Texas
Oncology Research and Development
Swarnali Acharyya, PhD GlaxoSmithKline
Research Fellow Philadelphia, Pennsylvania
Sloan-Kettering Institute
Robert C. Bast, Jr., MD
Memorial Sloan-Kettering Cancer Center
Vice President for Translational Research
New York, New York
Harry Carothers Wiess Distinguished University Chair for
Cancer Research
Bachir Alobeid, MD
Internist and Professor of Medicine
Professor of Clinical Pathology and Cell Biology
Departments of Experimental Therapeutics and Gynecologic
Program Director, Hematopathology Fellowship Training
Medical Oncology
Program
Division of Cancer Medicine
Department of Pathology and Cell Biology
The University of Texas M. D. Anderson Cancer Center
Columbia University Medical Center–College of Physicians
and Surgeons Houston, Texas
The New York Presbyterian Hospital
New York, New York
vii
viii Contributors
Stephen B. Baylin, MD Malcolm V. Brock, MD
Professor of Oncology Associate Professor of Surgery
Johns Hopkins University Associate Professor of Oncology
The Sidney Kimmel Comprehensive Cancer Center at Johns Director of Clinical and Translational Research in Thoracic
Hopkins School of Medicine Surgery
Baltimore, Maryland Johns Hopkins University School of Medicine
The Johns Hopkins Hospital
Joseph R. Bertino, MD
Baltimore, Maryland
Professor
Medicine and Pharmacology Nelson E. Brown, MD, PhD
University of Medicine and Dentistry of New Jersey Instructor of Medicine, Molecular Oncology Research Institute
Robert Wood Johnson Medical School Tufts Medical Center
Chief Scientific Officer Boston, Massachusetts
American Cancer Society Professor
Andrea Califano, Laureate in Physics
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey Clyde and Helen Wu Professor of Chemical Systems Biology
Columbia University
Govind Bhagat, MD Director
Professor of Pathology and Cell Biology JP Sulzberger Columbia Genome Center
Department of Medicine Columbia University
Division of Hematopathology New York, New York
Department of Pathology and Cell Biology
Columbia University Medical Center–College of Physicians George Adrian Calin, MD, PhD
and Surgeons Associate Professor
The New York Presbyterian Hospital Department of Experimental Therapeutics
New York, New York Division of Cancer Medicine
The University of Texas M. D. Anderson Cancer Center
Mina J. Bissell, PhD
Houston, Texas
Distinguished Scientist
Life Sciences Division Peter R. Carroll, MD
Lawrence Berkeley National Laboratory
Professor and Chair
Berkeley, California
Department of Urology
Ken and Donna Derr-Chevron Distinguished Professor
Scott A. Boerner, MS
Director of Clinical Services and Strategic Planning
Department of Internal Medicine
University of California–San Francisco
Wayne State University
Helen Diller Family Comprehensive Cancer Center
Barbara Ann Karmanos Cancer Institute
Associate Dean
Detroit, Michigan
University of California–San Francisco School of Medicine
Jessica E. Bolden, PhD San Francisco, California
Gene Regulation Laboratory
Chakra Chennubhotla, PhD
Peter MacCallum Cancer Centre
Assistant Professor
Melbourne, Australia
Department of Computational and Systems Biology
Ernest C. Borden, MD University of Pittsburgh Drug Discovery Institute
The Cleveland Clinic University of Pittsburgh
Taussig Cancer Institute Pittsburgh, Pennsylvania
Case Comprehensive Cancer Center
Cleveland, Ohio
Contributors ix
Toni K. Choueiri, MD Nancy E. Davidson, MD
Associate Professor of Medicine Hillman Professor of Oncology
Harvard Medical School Director
Attending Physician University of Pittsburgh Cancer Institute and
Dana-Farber Cancer Institute UPMC Cancer Center
Boston, Massachusetts Associate Vice Chancellor for Cancer Research
University of Pittsburgh
Christopher L. Corless, MD, PhD Pittsburgh, Pennsylvania
Professor of Pathology
April Davis, BS
Oregon Health and Science University
Research Technician
Chief Medical Officer
Comprehensive Cancer Center
Knight Diagnostic Laboratories
Department of Internal Medicine
Knight Cancer Institute
University of Michigan
Portland, Oregon
Ann Arbor, Michigan
Ana Luísa Correia, PhD
Changchun Deng, MD, PhD
Life Sciences Division
Assistant Professor of Medicine and Experimental Therapeutics
Lawrence Berkeley National Laboratory
Center for Lymphoid Malignancies
Berkeley, California
Department of Medicine
Rebecca Critchley-Thorne, PhD Division of Hematopathology
Department of Pathology and Cell Biology
Director
Columbia University Medical Center–College of Physicians
Biomarker and Diagnostic Development
and Surgeons
Cernostics, Inc.
The New York Presbyterian Hospital
Pittsburgh, Pennsylvania
New York, New York
Carlo Maria Croce, MD
J. Alan Diehl, PhD
The John W. Wolfe Chair in Human Cancer Genetics
J. Samuel Staub, MD, Endowed Professor
Chair
Department of Cancer Biology
Department of Molecular Virology, Immunology, and Medical
Perelman School of Medicine
Genetics
University of Pennsylvania
Director
Philadelphia, Pennsylvania
Human Cancer Genetics Program
The Ohio State University, Comprehensive Cancer Center John DiGiovanni, PhD
Columbus, Ohio Professor
Division of Pharmacology and Toxicology
Alan D. D’Andrea, MD
College of Pharmacy
Alvan T. and Viola D. Fuller American Cancer Society
The University of Texas at Austin
Professor
Professor
Harvard Medical School
Department of Nutritional Sciences
Department of Radiation Oncology
College of Natural Sciences, The University of Texas at Austin
Dana-Farber Cancer Institute
Austin, Texas
Boston, Massachusetts
x Contributors
Joseph Paul Eder, MD Christopher D. M. Fletcher, MD, FRC Path
Director of Experimental Therapeutics and the Phase I Professor
Research Group Department of Pathology
Yale Cancer Center and Smilow Cancer Hospital Harvard Medical School
Yale University School of Medicine Brigham and Women’s Hospital
New Haven, Connecticut Boston, Massachusetts
Suhendan Ekmekcioglu, PhD Cyrus M. Ghajar, PhD
Associate Professor Life Sciences Division
Department of Melanoma Medical Oncology Lawrence Berkeley National Laboratory
Division of Cancer Medicine Berkeley, California
The University of Texas M. D. Anderson Cancer Center
Houston, Texas Adam B. Glick, PhD
Associate Professor
Marc S. Ernstoff, MD
Center for Molecular Toxicology and Carcinogenesis
O. Ross McIntyre Professor of Medicine Department of Veterinary and Biomedical Sciences
Norris Cotton Cancer Center The Pennsylvania State University
Dartmouth-Hitchcock Medical Center University Park, Pennsylvania
Lebanon, New Hampshire
Geisel School of Medicine at Dartmouth Albert Gough, PhD
Hanover, New Hampshire Associate Professor
Department of Computational and Systems Biology
James R. Faeder, PhD
University of Pittsburgh Drug Discovery Institute
Associate Professor Pittsburgh, Pennsylvania
Department of Computational and Systems Biology
University of Pittsburgh Drug Discovery Institute Ramaswamy Govindan, MD
Pittsburgh, Pennsylvania Division of Oncology
Department of Medicine
Eric R. Fearon, MD, PhD
Alvin J. Siteman Cancer Center
Maisel Professor of Oncology Washington University School of Medicine
Division of Molecular Medicine and Genetics St. Louis, Missouri
Departments of Internal Medicine, Human Genetics, and
Pathology Jennifer R. Grandis, MD, FACS
University of Michigan School of Medicine Vice Chair for Research
Ann Arbor, Michigan Distinguished Professor of Otolaryngology and Pharmacology
University of Pittsburgh School of Medicine
Lydia W. S. Finley, PhD
Program Leader
Postdoctoral Fellow
Head and Neck Cancer Program
Cancer Biology and Genetics Program
University of Pittsburgh Cancer Institute
Memorial Sloan-Kettering Cancer Center
Pittsburgh, Pennsylvania
New York, New York
Susan Fisher, PhD
Professor
Department of Obstetrics, Gynecology and Reproductive Sciences
Eli and Edythe Broad Center of Regenerative Medicine and
Stem Cell Research
University of California–San Francisco
San Francisco, California
Contributors xi
Joe W. Gray, PhD David A. Guertin, PhD
Gordon Moore Endowed Chair Assistant Professor
Chairman Program in Molecular Medicine
Department of Biomedical Engineering University of Massachusetts Medical Center
Director Worcester, Massachusetts
OHSU Center for Spatial Systems Biomedicine
William C. Hahn, MD, PhD
Associate Director for Translational Research
Knight Cancer Institute Associate Professor of Medicine
Oregon Health and Science University (OHSU) Harvard Medical School
Portland, Oregon Chief
Division of Molecular and Cellular Oncology
Douglas R. Green, PhD Dana-Farber Cancer Institute
Peter C. Doherty Endowed Chair of Senior Associate Member
Immunology
Boston, Massachusetts
St. Jude Children’s Research Hospital
Cancer Program, Broad Institute of MIT and
Memphis, Tennessee Harvard
Cambridge, Massachusetts
Kirsten L. Greene, MD, MS
Associate Professor of Urology William N. Hait, MD, PhD
Vice Chair, Education
Global Head
Department of Urology
Janssen Research and Development
University of California–San Francisco
Raritan, New Jersey
Helen Diller Family Comprehensive Cancer Center
Veterans Affairs Medical Center Matthew C. Havrda, PhD
San Francisco, California Instructor in Pediatrics
Geisel School of Medicine at Dartmouth
Elizabeth A. Grimm, PhD
Hanover, New Hampshire
Professor
Norris Cotton Cancer Center
Department of Melanoma Medical Oncology
Dartmouth-Hitchcock Medical Center
Deputy Head for Research Affairs
Lebanon, New Hampshire
Division of Cancer Medicine
Frank McGraw Memorial Endowed Chair in Cancer Research Matthew L. Hedberg, MD/PhD Candidate
The University of Texas M. D. Anderson Cancer Center University of Pittsburgh School of Medicine
Houston, Texas Pittsburgh, Pennsylvania
Luca Grumolato, PhD
Roy S. Herbst, MD, PhD
Professor
Professor of Medicine and Pharmacology
Chair of Excellence INSERM
Chief of the Medical Oncology
Université de Rouen
Associate Director for Translational Science
Rouen, France
Yale University School of Medicine
Instructor, Department of Oncological Sciences
Yale Cancer Center
Mount Sinai School of Medicine
New Haven, Connecticut
New York, New York
Philip W. Hinds, PhD
Jian Gu, PhD
Professor
Assistant Professor
Molecular Oncology Research Institute
Department of Epidemiology
Tufts Medical Center
The University of Texas M. D. Anderson Cancer Center
Boston, Massachusetts
Houston, Texas
xii Contributors
Daniela Hoehn, MD, PhD Johanna A. Joyce, PhD
Assistant Professor of Clinical Pathology and Cell Biology Cancer Biology and Genetics Program
Department of Medicine Memorial Sloan-Kettering Cancer Center
Division of Hematopathology New York, New York
Department of Pathology and Cell Biology
William G. Kaelin, Jr., MD
Columbia University Medical Center–College of Physicians and
Surgeons Professor of Medicine
The New York Presbyterian Hospital Harvard Medical School
New York, New York Dana-Farber Cancer Institute
Boston, Massachusetts
Peter M. Howley, MD
Shattuck Professor of Pathological Anatomy Hagop Kantarjian, MD
Department of Microbiology and Immunobiology Department of Leukemia
Division of Immunology The University of Texas M. D. Anderson Cancer Center
Harvard Medical School Houston, Texas
Boston, Massachusetts
Brian Keith, PhD
Andrew C. Hsieh, MD Associate Investigator and Director of Education
Helen Diller Family Comprehensive Cancer Center Abramson Family Cancer Research Institute
University of California–San Francisco Medical Center Adjunct Professor
San Francisco, California Department of Cancer Biology
University of Pennsylvania
Patrick Hwu, MD
Philadelphia, Pennsylvania
Department of Melanoma Medical Oncology
Center for Cancer Immunology Research Ronan Kelly, MD, MBA
The University of Texas M. D. Anderson Cancer Center Assistant Professor of Oncology
Houston, Texas Johns Hopkins University School of Medicine
The Sidney Kimmel Comprehensive Cancer Center at Johns
Mark A. Israel, MD Hopkins School of Medicine
Director Baltimore, Maryland
Norris Cotton Cancer Center
Hasan Korkaya, PhD
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire Research Investigator
Professor of Pediatrics and Genetics Comprehensive Cancer Center
Geisel School of Medicine at Dartmouth Department of Internal Medicine
Hanover, New Hampshire University of Michigan
Ann Arbor, Michigan
Tyler Jacks, PhD
W. Michael Korn, MD
Director
Koch Institute for Integrative Cancer Research Associate Professor in Residence
David H. Koch Professor of Biology Department of Medicine
Investigator (Gastroenterology and Medical Oncology)
Howard Hughes Medical Institute University of California–San Francisco
Massachusetts Institute of Technology San Francisco, California
Cambridge, Massachusetts