Molecular Genetics of Colorectal Neoplasia: A Primer for the Clinician

187 Pages·2004·4.549 MB·English

by  James Church BSc, MBChB, Mmed Sci, FRACS, Graham Casey PhD (auth.)

MOLECULAR GENETICS OF COLORECTAL
NEOPLASIA:
A PRIMER FOR THE CLINICIAN
SECOND EDITION
DEVELOPMENTS IN ONCOLOGY
Volume 82
MOLECULAR GENETICS OF COLORECTAL
NEOPLASIA: A PRIMER FOR THE CLINICIAN
Second Edition
James Church, BSc, MBChB, Mmed Sci, FRACS
Victor W. F azio Chair in Colorectal Surgery
Director of the David G. Jagelman Inherited
Colorectal Cancer Registries
Department of Colorectal Surgery
The Cleveland Clinic Foundation
Cleveland, Ohio
and
Graham Casey, PhD
Section Head Colorectal Cancer Research
Associate Staff, Departments of Cancer Biology,
Colorectal Surgery and Obstetrics and Gynecology
The Cleveland Clinic Foundation
Lerner Research Institute
Cleveland, Ohio
SPRINGER SCIENCE+BUSlNESS MEDIA. LLC
Library of Congress Cataloging-in-Publication Data
Molecular genetics of colorectal neoplasia: a primer for the clinician / edited by James
Church, Graham Casey. __ 2nd ed.
p. ;cm.
Rev. ed. of: Molecular genetics of colorectal neoplasia / James M. Church, Bryan R.G.
Williams, Graham Casey. c 1996
Includes bibliographical references and index.
ISBN 978-1-4613-4765-1 ISBN 978-1-4419-9310-6 (eBook)
DOI 10.1007/978-1-4419-9310-6
1. Colon (Anatomy)--Cancer--Genetic aspects. 2. Rectum--Cancer--Genetic aspects. 3.
Colon (Anatomy)--Cancer--Molecular aspects. 4. Rectum--Cancer--Molecular aspects. 1.
Church, James, M. II. Casey, Graham. III. Church, James M. Molecular genetics and
colorectal neoplasia.
[DNLM: 1. Colorectal Neoplasms--genetics. 2. Molecular Biology--methods. WI 529
M7182oo3] RC280.C6C482oo3
616.99'4347042--dc22 2003061201
Copyright © 2004 by Springer Science+Business Media New York
Originally published by Kluwer Academic Publishers in 2004
Softcover reprint ofthe hardcover lst edition 2004
AII rights reserved. No part of this work may be reproduced, stored in a retrieval system,
or transmitted in any form or by any means, electronic, mechanical, photocopying,
microfilming, recording, or otherwise, without the written permission from the Publisher,
with the exception of any material supplied specificalIy for the purpose of being entered and
executed on a computer system, for exclusive use by the purchaser of the work.
Printed on acid-free paper.
DEDICATION
This book is dedicated to Mr. Eddie DeBartolo and his family,
10
grateful appreciation of his friendship,support and encouragement.
CONTENTS
CHAPTER 1. AN INTRODUCTION TO
<iENETIC~ 1
1.1 WHAT IS "GENETICS?"
WHAT IS "HEREDITY?" 1
1.2 BASICGENETICS 2
1.3 BASIC MOLECULAR GENETICS 7
REFERENCES ANDRECOMMENDED READING 11
CHAPTER 2. CHAN<iES IN
<iENE FUNCTION 13
2.1 MUTATIONS 13
2.2 MUTATIONS ANDINHERITANCE 17
2.3 DOMINANT VS RECESSIVE INHERITANCE 19
2.4 CAUSES OF MUTATIONS THAT UNDERLIE 21
LARGE BOWEL NEOPLASIA
2.5 REDUCTION OF EXPRESSION 22
REFERENCES ANDRECOMMENDED READING 24
Vlll
CHAPTER 3. MOLECULAR GENETICS 27
METHODS SIMPLIFIED
3.1 BASIC TECHNIQUES IN DNAANALySIS......•...•27
3.2 MUTATION ANALYSIS FOR INHERITED 35
DISORDERS
3.3 GENE EXPRESSION IN TUMORS ....................•.38
3.4 DETECTING HYPERMETHYLATION .40
3.5 RECOMBINANT DNATECHNOLOGy .41
3.6 THE HUMAN GENOME PROJECT 42
3.7 TISSUEBANKS 43
RECOMMENDED READING......................•............43
CHAPTER 4. GENES AND CELL 45
HOMEOSTASIS
4.1 SOME DIFFERENCES BETWEEN 45
CULTURED NORMAL CELLS AND
CANCER CELLS
4.2 REGULATION OF CELL GROWTH .46
4.3 APOPTOSIS OR PROGRAMMED..............•.......55
CELL DEATH
REFERENCES ANDRECOMMENDED READING 56
IX
CHAPTER 5. PATHOLOGY OF..........••......•.57
COLORECTAL NEOPLASIA
5.1 WHAT IS NEOPLASIA? 57
5.2 WHAT IS DYSPLASIA? 57
5.3 WHAT IS ANADENOMA? 59
5.4 WHAT IS A CARCINOMA? 62
5.5 HOW DO COLORECTAL NEOPLASMS 63
EVOLVE?
5.6 COLORECTAL "FERTILITY" FOR 64
NEOPLASIA
5.7 HAMARTOMATOUS POLYPS 65
~1f~1t~~~~~ 66
CHAPTER 6. MOLECULAR GENETICS OF.....69
COLORECTAL NEOPLASIA
6.1 THE ADENOMA - CARCINOMA SEQUENCE.....69
6.2 THE GENES INVOLVED IN 70
COLORECTAL NEOPLASIA
6.3 DNA REPAIR 76
6.4 SIGNAL TRANSDUCTION CASCADES, 82
GENETIC EVENTS ANDTHE TWO GENETIC
ROUTES TO COLORECTAL NEOPLASIA
x
6.5 TELOMERES ANDTELOMERASE 86
REFERENCES ANDRECOMMENDED READING •••••••••••87
CHAPTER 7. FAMILY HISTORY: THE.........•.91
KEY THAT UNLOCKS THE DOOR
TO FAMILIAL COLORECTAL CANCER
7.1 THE SIGNIFICANCE OF A FAMILY............••••91
HISTORY OF COLORECTAL NEOPLASIA
7.2 DEFINING LEVEL OF RISK.....................•.....93
7.3 SCREENING HIGH RISK FAMILIES 95
7.4 HOW TO TAKE A FAMILY HISTORY 97
ANDHOW TO INTERPRET THE RESULTS
7.5 THE FAMILY TREE...........•.•..........•.....••.....98
REFERENCES AND RECOMMENDED READING •••••••••101
CHAPTER 8. PATIENTS ANDTHEIR .••...•....103
FAMILIES WITH A FAMILY HISTORY
OF COLORECTAL CANCER
8.1 EDUCATION 103
8.2 COUNSELING 105
REFERENCES ANDRECOMMENDED READING ...107
Xl
CHAPTER 9. INHERITED SYNDROMES: I09
FAMILIAL ADENOMATOUS POLYPOSIS,
HEREDITARY NON POLYPOSIS
COLORECTAL CANCER, AND THE
HAMARTOMATOUS POLYPOSES
9.1 FAMILIAL ADENOMATOUS POLYPOSIS 109
9.2 DUODENAL NEOPLASIA 118
9.3 DESMOID TUMORS 119
9.4 OTHER TUMORS 121
9.5 ATTENUATED POLYPOSIS (AAPC) 122
9.6 FAP AND HNPCC 122
9.7 HEREDITARY NON POLYPOSIS 123
COLORECTALCANCER
9.8 THE HAMARTOMATOUS POLYPOSES 129
REFERENCES ANDRECOMMENDED READING .....•••.134
CHAPTER 10. A REGISTRY FOR 139
INHERITED COLORECTAL CANCER
10.1 DEFINITION 139
10.2 ROLES OF A REGISTRy 139
10.3 STARTING A REGISTRY 143
10.4 HIPAA ANDITS IMPLICATIONS FOR 146
REGISTRY RESEARCH