Molecular Biology of Cancer - Second Edition

Molecular Biology of Cancer, Second Editionby F. Macdonald, C. H. J. Ford & A. G. CassonMolecular Biology of CancerSecond editionF. MacdonaldRegional genetics Service, Birmingham Womens Hospital, QueenElizabeth Hospital,Birmingham, UKC H.. FordDepartment of Surgery, Kuwait University, KuwaitA.G. CassonDepartment of Surgery, Dalhousie University, Halifax, NovaScotia. CanadaBIOS Scientific PublishersTaylor &Francis GroupLONDON AND NEW YORKo Garland Science/BIOS Scientific Publishers 2004First published 2004This edition published in the Taylor Francis e-Library, 2005To purchase your own copy of this or any of Taylor Francis or Routledge's collection of thousands of e Books pleasegotowww.ebooKstore.tandf.co.uk.All rights reserved. No part of this book may be reprinted or reproduced or utilised in any form or by any electronicmechanical, or other means, now known or hereafter invented, including photocopying and recording, or in anyinformation storage or retrieval system, without permission in writing from the publishersA CIP catalogue record for this book is available from the British Library.isbN 0-203-50344-9 Master e-book isbnISBN 0-203-59747-8(Adobe eReader Format)ISBN 1-85996-247-5(Print Edition)Garland Science/BIoS Scientific Publishers4 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN, UK and29 West 35th Street. New York. NY 10001-2299 USAWorldWideWebhomepagewww.garlandscience.comGarland Science/BIOS Scientific Publishers is a member of the Taylor Francis GroupLibrary of Congress Cataloging-in-Publication DataMacdonald. FMolecular biology of cancer/Macdonald, Ford Casson-[2nd ed Ip cm.Includes bibliographical references and indexISBN1-85996-247-5(pbk.)1. Cancer-Molecular aspects 2. Cancer-Genetic aspects, 3. Cancer-Molecular diagnosisI. Ford. C.H.J. II. Casson. Alan G. Ill. TitleRC2684M23200461699′4042dc222004001336Production Editors: Georgia Bushell and Harriet MillesContentsAbbreviationsXIVPrefaceXIX1 General principles1.1 Introduction1. 2 What is cancer?1. 3 The cell cycle1. 4 Apoptosis1.5 Chromosomes and cancer24661.6 Inherited vs. sporadic cancer1.7 The multistage nature of cancer development10References102 Oncogenes122.1 Viruses and cancer2.2 Cellular oncogenes132.2.1 Function of the proto-oncogenes162.2.2 Mechanisms of oncogene activation262.3 Oncogenes in human tumors29References103 Tumor suppressor genes333.1 Introduction333.2 Evidence for the existence of tumor suppressor genes353.2.1 Suppression of malignancy by cell fusion353.2.2 Tumor suppressor genes in hereditary cancers: the retinoblastoma model363.3 Retinoblastoma-RBI393.3.1 Cell cycle regulation of rB403.3.2 RB/E2F pathway3.3.3RB and apoptosis423. 3. 4 RB in human cancers4334TP53(53)3.4.1 The tp53 gene and its protein product p533.4.2 Activation of TP53453.4.3 Activated p53 responses--cell cycle inhibition473.4.4 Activated p53 responses- apoptosis483.4.5 Other functions of activated p53483.4.6 Mutations of p53493.5 APC503.5./ The apc gene and its protein product503.5.2 Function of the APC protein513.5.3 Mutations in aPC533.6 BRCAI and BRCA2533.6./ The brCal and 2 genes and their protein products543.6.2 Mutations in brcal and 2563.7 WTI563. 8 NFl and NF2573.8.1NFl573.8.2NF2583.9 VHL593.10 TSCI and TSC2593.11 PTCH3. 12 Interaction and differences between oncogenes and tumor suppressor genesReferences614 Cell cycle control genes and mismatch repair genes4.1 Introduction4.2 Cyclins and cyclin-dependent kinases4.3 Cyclin-dependent kinase inhibitors674.4 Progression and control of the cell cycle684.5 Cyclins CDKs and cKIs in cancer714.6 Mismatch repair genes72References755 Hereditary cancers775.1 Introduction5.2 Inherited cancer syndromes7785.3 Procedures for genetic testing5.4 Familial colon cancer785.4.1 Familial adenomatous polyposis(FAP)795.4.2 Hereditary nonpolyposis colon cancer(HNPCC)825.4.3 Other syndromes predisposing to colorectal cancer855.5 Familial breast and breast/ovarian cancer875.5. BRCAl and bRCA2875.5.2 Other syndromes predisposing to breast cancer895.6 Li-Fraumeni syndrome (LFs)905.7 Multiple endocrine neoplasia905.7./ Multiple endocrine neoplasia type /(MENI)905.7.2 Multiple endocrine neoplasia type 2 (MEN2)915.8 Von Hippel Lindau syndrome (Vhl)925.9 Familial renal cell cancer925.10 Familial par ganglioma935.11 Neurofibromatoses935.11.1 Neurofibromatosis type /(NF1)935.11.2 Neurofibromatosis type 2 (NF2945. 12 Gorlin syndrome955.13 Tuberous sclerosis965.14 Familial gastric cancer965.15 Familial melanoma975.16 Hereditary prostate cancer985.17 Conclusion98References986 Lung cancer1026.1 Introduction1026.2 Pathology1026.2./ Small-cell lung cancer(SCLC)1036.2.2 Nonsmall-cell lung cancer(SCLC)1036.3 Clinical features1076. 4 Genetic factors and individual susceptibility1076.5 Molecular alterations in lung cancer1086.6 Tumor suppressor genes1096.7 Oncogenes1116.8 Growth factors and receptorsl116.9 Mesothelioma1126.10 Multiple primary tumors of the upper aerodigestive tract1126. 11 Implications for therapy112References1137 Colorectal cancer1157.1 Introduction1157.2 The adenoma- carcinoma sequence1157.3 Genetic changes in sporadic colorectal cancer-the role of oncogenes1177.3.1MYC1177.3.2RAS1187.3.3 Other oncogenes1197.4 Genetic changes in sporadic colorectal cancer-the role of tumor suppressor genes1207.4.p531207.4.2 Adenomatous polyposis coli gene(APC)1217.4.3 SMAD1227.4.4MCC12374.5NM231237.4.6 Other changes1237.5 Mismatch repair defects1237.6 TGF1247.7 Cell cycle regulators124References1258 Gastrointestinal cancer1288.1 Introduction1288.2 Pathology of esophagogastric cancer1288.2.1 Esophageal cancer1288.2.2 Barrett's esophagus1298 2.3 Gastric cancer1308.3 Epidemiology of esophagogastric malignancy1308. 4 Cellular and molecular alterations in esophagogastric cancer1328.4./ Cell cycle regulation1338.4.2 Epithelial proliferation markers1338.4.3 Aneuploidy1348. 4. 4 Chromosomal aberrations1348.4.5 Loss of heterozygosity1348.5 Tumor suppressor genes1358.5.p531358.5.2 Retinoblastoma(rB)1378.5.31388.54141388.5.5 Fragile histidine triad(FHit)gene1388.5.6 Adenomatous polyposis coli(APC) gene1398.6 Growth factors and receptors1398.7 Oncogenes1408.7.1 Cyclin D/1408.7.2RAS1408.8 DNA repair-associated genes1408.8./ Microsatellite instability1418.9 Hereditary factors1418.10 Cancers of the small intestine1428.11 Pancreatic cancer1428. 12 Hepatobiliary cancer1438/2./ Hepatocellular carcinoma1438.12.2 Intrahepatic cholangiocarcinoma1438.12.3 Extrahepatic bile duct and gallbladder cancer8. 12. 4 HepatoblastomaReferences9 Breast cancer1489.1 Introduction1489. 2 Genetic changes in breast cancer1499.2.1MYC1499.2.2 erBB2 and RAS1519.2.3p531539.2.4 brCal and bRCA21559.2.5CCND11589.2.6RBl1589.2.7 Other chromosomal abnormalities and potential tumor suppressors1589.3 Estrogens and cell cycle regulation1599.4 Male breast cancer1609.5 Gene expression profilin160References16110 Genitourinary cancer16410.1 Ovarian and endometrial cancers16410.2 Cervical cancer16810.3 Testicular cancer17010.4 Renal cell cancer and bladder cancer170