Molecular Genetics of Cancer

537 Pages·2001·29.937 MB·\537

by  John Cowell (Editor)

Molecular Genetics
of Cancer
Second edition
The HUMAN MOLECULAR GENETICS series
Series Advisors
D.N. Cooper, Institute of Medical Genetics, University of Wales College of
Medicine, Cardiff, UK
S.E. Humphries, Division of Cardiovascular Genetics, University College
London Medical School, London, UK
A. Woiffe, Sangamo Biosciences Inc, Point Richmond Tech Center, Richmond,
CA, USA
Human Gene Mutation
From Genotype to Phenotype
Functional Analysis of the Human Genome
Environmental Mutagenesis
HLA and MHC: Genes, Molecules and Function
Human Genome Evolution
Gene Therapy
Molecular Endocrinology
Venous Thrombosis: from Genes to Clinical Medicine
Protein Dysfunction in Human Genetic Disease
Molecular Genetics of Early Human Development
Neurofibromatosis Type 1: from Genotype to Phenotype
Analysis of Triplet Repeat Disorders
Molecular Genetics of Hypertension
Human Gene Evolution
Analysis of Multifactorial Disease
Transcription Factors
Molecular Genetics of Cancer, Second edition
Molecular Genetics
of Cancer
Second edition
J. K. Cowell
Department of Cancer Genetics, Roswell Park Cancer Institute,
Buffalo, NY 14263, USA
Taylor & Francis
Taylor &Francis Group
LONDON AND NEW YORK
CO Taylor & Francis Publishers Limited, 2001
First published in 1995 (1-872748-09-0)
Second edition 2001 (1-85996-169-x)
All rights reserved. No part of this book may be reproduced or transmitted, in any
form or by any means, without permission.
A CIP catalogue record for this book is available from the British Library.
ISBN 1 85996 169 x
Published by Taylor & Francis,
2 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN
270 Madison Ave, NewYork NY 10016
Transferred to Digital Printing 2008
Production Editor: Andrea Bosher
Typeset by Saxon Graphics Ltd, Derby, UK.
Publisher's Note
The publisher has gone to great lengths to ensure the quality of this reprint but points
out that some imperfections in the original may be apparent
Contents
(cid:9)
Contributors ix
(cid:9)
Abbreviations xi
(cid:9)
Preface xv
1. Basic principles in cancer genetics.1K. Cowell (cid:9) 1
Introduction(cid:9) 1
Cytogenetics of cancer (cid:9) 2
The evolution of molecular cytogenetics(cid:9) 5
Genetic linkage and the identification of hereditary cancer genes(cid:9) 7
The two-hit hypothesis(cid:9) 9
Loss of heterozygosity(cid:9) 10
Oncogenes(cid:9) 13
Somatic cell hybrids(cid:9) 15
HTF islands and long range maps(cid:9) 19
Construction of physical maps of the genome(cid:9) 20
Specialized genomic libraries and positional cloning(cid:9) 22
cDNAs and ESTs(cid:9) 25
Mutation analysis(cid:9) 26
Summary(cid:9) 27
2. Defining genetic changes associated with cutaneous malignant melanoma(cid:9) 33
M. U. Faruque and 1.M. Trent
Introduction(cid:9) 33
Development and biology of melanocytes(cid:9) 33
Epidemiology(cid:9) 34
Clinical characteristics and pathology(cid:9) 37
Genetics of melanoma(cid:9) 37
Genes and melanoma(cid:9) 41
3. The genetics of breast and ovarian cancer. Pj. Neville, S.J. Morland,(cid:9) Vaziri(cid:9) 53
and G. Casey
Introduction(cid:9) 53
Hereditary breast and ovarian cancer syndromes(cid:9) 53
Non hereditary breast and ovarian cancer (cid:9) 60
Conclusions(cid:9) 69
4. Genetics of von Hippel-Lindau disease. E.R. Maher (cid:9) 81
Introduction(cid:9) 81
Clinical aspects(cid:9) 81
VHL disease and isolated features of VHL disease(cid:9) 83
Molecular genetics of VHL disease(cid:9) 84
Genotype—phenotype(cid:9) 85
VHL and sporadic tumorigenesis(cid:9) 86
VHL and development(cid:9) 87
VHL gene function(cid:9) 87
Conclusion(cid:9) 90
5. Genetics of NFl and NF2. M.R. Wallace and M. MacCollin(cid:9) 95
History and nomenclature of NFl and NF2(cid:9) 95
Clinical features of NFl(cid:9) 95
V
VI CONTENTS
Genetics of NF1(cid:9) 97
NF1 tumor genetics(cid:9) 101
NF2 clinical and genetic information(cid:9) 103
The NF2 gene and protein(cid:9) 103
Germline NF2 mutations(cid:9) 104
The NF2 gene is a tumor suppressor (cid:9) 105
Conclusions and future directions(cid:9) 106
6. Genetics of gastric cancer. WM. Grady(cid:9) 115
Introduction(cid:9) 115
Genetic alterations and gastric carcinogenesis(cid:9) 116
Genomic instability and gastric cancer (cid:9) 120
Specific genetic alterations in gastric cancer (cid:9) 123
Epigenetic alterations in gastric cancer (cid:9) 135
Conclusions(cid:9) 136
7. Multiple endocrine neoplasia type I. B.T. Teh(cid:9) 149
Introduction(cid:9) 149
Clinical manifestations(cid:9) 149
Positional cloning of the MEN1 gene(cid:9) 150
The MENI gene(cid:9) 151
The functions of the MEN1 gene(cid:9) 151
Homologous genes(cid:9) 153
MEN1 mutations(cid:9) 153
Genotype—phenotype correlation(cid:9) 159
Mitogenic factors and chromosome instability(cid:9) 163
Conclusions(cid:9) 164
8. Multiple endocrine neoplasia type 2. C. Eng(cid:9) 171
Introduction(cid:9) 171
Clinical features of MEN 2(cid:9) 171
Genetics of MEN 2(cid:9) 172
Germline RET mutations in Hirschsprung disease(cid:9) 177
Clinical management of individuals at risk(cid:9) 178
The RET proto-oncogene(cid:9) 180
Animal models(cid:9) 185
The triumph of molecular oncology and the dilemma of penetrance and(cid:9) 186
expressional modification
9. TP53 in cancer origin and treatment. E.A. Komarova, P.M. Chumakov and (cid:9)195
A.V. Gudkov
Introduction(cid:9) 195
TP53 gene structure and regulation(cid:9) 195
Cell growth control by TP53(cid:9) 198
Mechanisms of TP53 regulation(cid:9) 204
TP53 in the organism(cid:9) 208
TP53 in the tumor (cid:9) 211
TP53 and cancer treatment (cid:9) 216
10. Colorectal cancer. P.D. Chapman and J. Burn(cid:9) 233
Introduction(cid:9) 233
Family history and CRC risk (cid:9) 233
Genetic factors predisposing to CRC(cid:9) 234
Inherited CRC predisposition(cid:9) 236
Modifiers and genes of minor effect; allelic variants(cid:9) 242
Personal history and risk(cid:9) 245
Prevention(cid:9) 246
Social considerations(cid:9) 248
Conclusions(cid:9) 249
CONTENTS VII
11. Genetics of prostate cancer. T Kainu and W Issues(cid:9) 255
Introduction(cid:9) 255
Somatic genetic changes in prostate cancer development(cid:9) 255
Inherited susceptibility to prostate cancer — overview(cid:9) 258
Epidemiological evidence for the presence of prostate cancer susceptibility genes(cid:9) 259
Segregation analyses(cid:9) 260
Linkage studies(cid:9) 261
Association analyses(cid:9) 266
Possible correlations of phenotype and genotype(cid:9) 268
12. Tuberous sclerosis complex. M. Nellist, S. Verhoef, D. Lindhout, D.15.Halley(cid:9) 277
and A.M.W van den Ouweland
Clinical aspects of tuberous sclerosis complex(cid:9) 277
Genes involved in tuberous sclerosis complex(cid:9) 281
Functional characterization of the TSC I and TSC2 gene products(cid:9) 285
Genetic counseling for TSC(cid:9) 291
13. Retinoblastoma: patients, tumors, gene and protein contribute to the(cid:9) 297
understanding of cancer. A.S. Duckett, L. Dagnino and B.L. Gallie
Introduction(cid:9) 297
Retinoblastoma tumors and the RBI gene(cid:9) 298
Therapy of retinoblastoma(cid:9) 301
Disruption of the RB pathway in neoplasia(cid:9) 303
Cellular function of pRB(cid:9) 305
Summary(cid:9) 311
14. Genetics of Wilms tumor. M.A.E. Frevel and B.R.G. Williams(cid:9) 317
Introduction(cid:9) 317
The 11p13 locus and the Wilms tumor suppressor gene, WT1(cid:9) 318
The 11p15 locus and loss of imprinting in Wilms tumor (cid:9) 324
Other genetic loci associated with Wilms tumor (cid:9) 326
Conclusions(cid:9) 327
15. Genetics of neuroblastoma. j.M.Maris and G.M. Brodeur (cid:9)335
Introduction(cid:9) 335
Neuroblastoma predisposition(cid:9) 336
Loss of genetic material and inactivation of tumor suppressor genes(cid:9) 338
Gain of genetic material and oncogene activation(cid:9) 342
Alterations in gene expression(cid:9) 346
Genetic model of neuroblastoma development (cid:9) 349
16. Genetics of brain tumors. B.K. Ahmed Rasheed, R.N. Wiltshire, S.H. Bigner (cid:9)363
Introduction(cid:9) 363
Astrocytomas(cid:9) 363
Oligodendrogliomas(cid:9) 369
Ependymomas(cid:9) 372
Medulloblastomas(cid:9) 373
Meningioma and schwannoma(cid:9) 375
Atypical teratoid/rhabdoid tumors(cid:9) 376
Summary(cid:9) 376
17. Molecular genetics of lung cancer. F.J. Kaye and A. Kubo(cid:9) 387
Introduction(cid:9) 387
Histologic types of lung cancer (cid:9) 388
Cytogenetics of lung cancer (cid:9) 390
Recessive genes frequently targeted in lung cancer (cid:9) 391
Dominant oncogenes in lung cancer (cid:9) 399
Therapeutic considerations(cid:9) 401
Conclusions(cid:9) 403
VIII CONTENTS
18. Genetics of liver cancer. A.-M. Hui, L. Sun and M. Makuuchi(cid:9) 415
Introduction(cid:9) 415
Pathogenesis(cid:9) 415
Tumor suppressors and cyclin-dependent kinase inhibitors(cid:9) 416
Oncogenes(cid:9) 422
Allelotype(cid:9) 423
DNA methylation(cid:9) 424
Tumors of multifocal origin and intrahepatic metastases(cid:9) 426
A molecular model of human hepatocarcinogenesis(cid:9) 428
19. The genetics of bladder cancer. M.A. Knowles(cid:9) 435
Introduction(cid:9) 435
Etiology and epidemiology(cid:9) 436
Chromosomal alterations in TCC(cid:9) 437
Oncogenes involved in TCC development(cid:9) 438
Tumor suppressor genes involved in TCC development (cid:9) 443
A model for TCC progression(cid:9) 449
Genetics of schistosomiasis-associated bladder cancer (cid:9) 451
Conclusion(cid:9) 452
20. Genetics of rhabdomyosarcoma. J. G. Pressey and EG.Barr (cid:9)461
Introduction(cid:9) 461
Chromosomal translocations in ARMS(cid:9) 461
11p15 allelic loss in ERMS(cid:9) 464
Other genetic changes in RMS(cid:9) 466
Altered pathways in sporadic RMS and inherited cancer predisposition syndromes(cid:9) 467
RMS mouse models(cid:9) 473
Conclusions(cid:9) 475
21. Role of telomeres and telomerase in aging and cancer./ W Shay, W.E. Wright (cid:9)483
and R.A. Schultz
Intrcduction(cid:9) 483
Chromosome instability syndromes and telomere metabolism(cid:9) 488
Telomere shortening in mice(cid:9) 497
Future applications for telomerase as a product to extend cell life span(cid:9) 498
Telomerase in cancer diagnostics(cid:9) 499
Telomerase in cancer therapeutics(cid:9) 500
Conclusions(cid:9) 503
Index(cid:9) 509
Contributors
Ahmed Rasheed, B.K. Department of Pathology, Duke University Medical Center,
Durham NC 27710, USA
Barr, F.G. Department of Pathology and Laboratory Medicine, University of
Pennsylvania School of Medicine, Philadelphia PA 19104-6-82, USA
Signer, S.H. Department of Pathology, Duke University Medical Center, Durham NC
27710, USA
Burn, J. School of Biochemistry and Genetics, Department of Genetics, University of
Newcastle, Newcastle-upon-Tyne, NE2 4AA, UK
Casey, G. Cleveland Clinic Foundation, Lerner Research Institute, Cancer Biology
Department NB40, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Chapman, P.D. School of Biochemistry and Genetics, Department of Genetics,
University of Newcastle, Newcastle-upon-Tyne, NE2 4AA, UK
Chumakov, P.M. Department of Molecular Genetics (M/C 669), University of Illinios
at Chicago, 900 South Ashland Avenue, Chicago, IL 60607-7170, USA
Cowell, J.K. Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo,
NY 14263, USA
Dagnino, L. Department of Pharmacology and Toxicology and Lawson Health
Research Institute, The University of Western Ontario, London, Ontario, Canada
Duckett, A.S. Laboratory of Molecular Signalling, Department of Zoology,
University of Cambridge, Cambridge, UK
Eng, C. Director, Clinical Cancer Genetics Program, The Ohio State University, 420
W 12th Avenue, Suite 690 TMRF, Columbus, OH 43210, USA
Faruque, M.U. National Human Genome Research Institute, 9000 Rockville Pike,
Bethesda MD 20892-4094, USA
Frevel, M. Cleveland Clinic Foundation, Lerner Research Institute, Cancer Biology
Department NB40, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Gallie, B.L. Departments of Opthalmology and Molecular and Medical Genetics and
the Divisions of Cancer Informatics and Cellular and Molecular Biology, Ontario
Cancer Institute, Princess Margaret Hospital, University of Toronto, Toronto,
Canada
Grady, W.M. Vanderbilt University Medical Center, Division of Gastroenterology,
1161 21st Ave. South, Nashville, TN 37232-2279, USA
Gudkov, A.V. Department of Molecular Genetics (M/C 669), University of Illinios at
Chicago, 900 South Ashland Avenue, Chicago, IL 60607-7170, USA
Halley, D.J.J. Department of Clinical Genetics, Erasmus University and Academic
Hospital Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
Hui, A.-M. Hepato-Biliary-Pancreatic Surgery Division, Departments of Surgery,
Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku,
Tokyo 113-0033, Japan
Issacs, W. James Buchanan Brady Urological Institute, The John Hopkins Hospital,
Baltimore, MD 21287, USA
Kainu, T. National Human Genome Research Institute, National Institutes of Health,
Bethesda, MD 20892, USA
Kaye, F.J. Medicine Branch, Bldg. 8, Rm. 5101, National Naval Medical Center,
Bethesda MD 20889, USA
ix