ADVANCESINCANCERRESEARCH VOLUME 54 This Page Intentionally Left Blank ADVANCES IN CANCER RESEARCH Edited by GEORGE F. VANDE WOUDE NCI-Frederick Cancer Research Facility Frederick, Maryland GEORGE KLEIN Department of Tumor Biology Karolinska lnstitutet Stockholm, Sweden Volume 54 ACADEMIC PRESS, INC. Harcourt Brace Jovanovich, Publishers San Diego New York Berkeley Boston London Sydney Tokyo Toronto This book is printed on acid-free paper. @ COPYRIGHT 0 1990 BY ACADEMIC PRESS, 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 photocopy, recording, or any information storage and remeval system, without permission in writing from the publisher. ACADEMIC PRESS, INC. San Diego, California 92101 Unrfad Kingdom Edmon published by ACADEMIC PRESS LIMITED 24-28 Oval Road, London NW 1 7DX LIBRARY OF CONGRESS CATALOG CARD NUMBER: ISBN 0-12-006654-8 (alk. paper) PRINTED IN THE UNITED STATES OF AMERICA LK1919293 9 8 7 6 5 4 3 2 1 52-13360 CONTENTS CONTRIBUTORS TO VOLUME 51......................................................................... xi The Role of DNA Methylation in Cancer PETERA . JONES AND JONATHAN D . BUCKLEY I. I1. I11. IV. V. VI . VII . VIII . IX. X. Introduction ................................................................................................. CpG Islands ................................................................................................. Transduction of the Methylation Signal .................................................... DNA Methylation in Tumor Cells ............................................................. Methylation in Uncultured Tumor Tissue ................................................ Effects of Chemical Carcinogens on DNA Methylation........................... Role of DNA Methylation in Tumor Diversification ................................ DNA Methylation during Oogenesis and Spermatogenesis .................... DNA Methylation and Genomic Imprinting ............................................. Conclusion ................................................................................................... References., .................................................................................................. 1 2 4 7 9 11 13 14 16 19 19 Genetic and Epigenetic Losses of Heterozygosity in Cancer Predisposition and Progression HEIDIJ . SCRABLE.CARMEN SAPIENZA.AND WEBSTERK. CAVENEE I. I1. 111. IV. V. VI . Introduction ................................................................................................. Genetics and Predisposition ....................................................................... Loss of Heterozygosity and Tumor Progression ....................................... Loss of Heterozygosity in Mixed Cancer................................................... Epigenetic Inactivation of Alleles in Human Cancer............................... Conclusions .................................................................................................. References .................................................................................................... V 25 29 37 42 49 58 59 vi CONTENTS Genetic and Molecular Studies of Cellular Immortalization JAMES R. SMITHAND OLIVIA M. PEREIKA-SMITH I. 11. Introduction ..................................................................... Short-Tenn Analysis of Cell Fusion Products ........................................... \‘. Discussion .....