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ClinicalCancerResearch

June 1997 #{149}Volume 3 Number 6pp. 829-1024 #{149}ISSN 1078-0432

AACR SPECIAL CONFERENCE IN CANCER RESEARCH

aacr@aacr.org (E-mail)http://www.aacr.org

DNA Methylation, Imprinting, and theEpigenetics of Cancer

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December 12-16, 1997El Conquistator Resort and Country Club

Las Croabas, Puerto RicoCONFERENCE CHAIRPERSONS

Peter A. Jones / Los Angeles, CAStephen B. Baylin I Baltimore, MD

Timothy Bestor I Columbia, NY

SCIENTIFIC PROGRAM

Keynote AddressArthur D. Riggs / Duarte, CA

Tumor Suppressor GenesStephen B. Baylin / Baltimore, MDCurtis C. Harris / Bethesda, MDWebster K. Cavenee I La Jolla, CASusan J. Clark / Sydney, Australia

Methylation PatternsTimothy Bestor / Columbia, NYJean-Pierre Jost I Basel, SwitzerlandSamuel H. Speck / St. Louis, MOCarl W. Schmid / Davis, CA

Mouse ModelsRudolf Jaenisch I Cambridge, MATyler Jacks / Cambridge, MAWilliam F. Dove I Madison, WISteven A. Belinsky / Albuquerque, NM

ImprintingDenise P. Barlow / Amsterdam, The NetherlandsAndrew P. Feinberg I Baltimore, MDMonica Peacocke / New York, NYAnthony E. Reeve I Dunedin, New Zealand

Chromatin StructuresAdrian P. Bird I Edinburgh, ScotlandAlan P. Wolffe I Bethesda, MDSteven Henikoff I Seattle, WA

Mismatch Repair and MethylationDonald Kohn I Los Angeles, CAChristoph Lengauer I Baltimore, MDJean-Pierre J. Issa I Baltimore, MD

Methylation and MutationJoseph Jiricny I Zurich, SwitzerlandGerd P. Pfeifer I Duarte, CAPeter A. Jones I Los Angeles, CA

Applicants are encouraged to submit abstractsfor poster presentation.

Application deadline: September 30, 1997

Information and Application Forms

American Association for Cancer Research

Public Ledger Building, Suite 826

150 South Independence Mall West

Philadelphia, PA 19106-3483

215-440-9300 215-440-9313 (FAX)

Editor-in-ChiefJohn Mendelsohn

Cell proliferation and death-prec’linical, and clinical trials:

radiation t/iera/)V. surgery, and subspec’ialtv investigation

Deputy EditorWaun Ki Hong

Clinical trials targeted at specific’ malignancies.

American Association frrCancer Research, Inc.

Executive Director andDirector of PublicationsMargaret Foti

!‘ublieatio,,s Suiff

Associate Director of PublicationsMary Anne Mennite

Manager. Editorial ServicesHeide M. Pusztav

Staff EditorsMichael J. BevendgeKathleeti C. Assenmacher

Pamela R. ArnoldLaurie B. BakerRonald M. Vitale

Staff AssistantMary Ellen Pining

Administrative CoordinatorHolly M. Haskins

Senior Editorial AssistantTheresa A. Griffith

Editorial AssistantsValerie L. Samuel

Andrea Conrad

Cecilia Gallo

Marketing CoordinatorRobert B. O’Malley

clu’mnoprevc’ntion

David R. Spriggs

P,’ec’linical pharmna(ologv. plicirmnacolo,t,’ical

clinical trialsDavid Sidransky

i%’Iole(’ular pat/zogene.si.s, mnolec’ula,’ com’relate.s

� Paul Sondel

Imnmnunotlierapv amid cvtokimies-pre(’limzi(’al. amid

I clinical trial.s�

Editorial Office

� Colleen M. Huhona. E.veci�tive Editor. Department of Educational Publishing Services-227. ‘The tltiiversity of Texas Nil).

I Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030. Phone: (713) 792-6014: Fax: (713) 792.6016.

ClinicalCancerResearch

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An Official Journalof theAmerican AssociationforCancer Research

Ad,ni,tistrative Staff

Director of AdministrationAdam D. Blistein

ControllerJoan D. Ritchie

Coordinator, FinancialOperations

George L. Moore

Manager, Meetings and ExhibitsJeffrey M. Ruben

Meeting PlannerCarole L. Kanoff

Public Information CoordinatorJenny Anne Horst-Martz

Assistant to the Executive DirectorRuth F. Fortson

Membership DevelopmentCoordinator

Robin E. Felder

Administrative AssistantMargaret A. Pickels

Systems SpecialistLydia I. Rodriguei

SecretaryMalika L. Wright

Editorial AssistantDiana F. Certo

Office ClerkJames J. Waters

Data Entry ClerkRobert A. Sinims II

Senior EditorsLance A. Liotta

Pathology, metastasis

Associate Editors

Martin D. AbeloffCarmen J. AllegraJames 0. Armitage

Laurence H. Baker

Charles M. Balch

Barthel Barlogie

Robert C. Bast. Jr.

Cohn B. Begg

Joseph R. Bertino

Clara D. Bloomfield

Ronald I-I. Blum

George J. Bosh

Paul A. Bunn, Jr.

Michael A. Caligiuri

Alfred E. Chang

Paul B. Chapman

Michaele C. Christian

Curt I. Civin

Ronald Crystal

William S. Dalton

Albert B. Deisseroth

Patricia K. Donahoe

Ross C. Donehower

Timothy J. Eberlein

Merrill J. Egorin

Frederick R. Eilber

Robert M. Elashoff

Paul F. Engstrom

Eric R. Fearon

Isaiah J. Fidler

Richard M. Fox

Michael A. Friedman

Zvi Y. Fuks

Stephen L. George

Giuseppe Giaccone

Luca Gianni

Anna Giuhiano

Eli Glatstein

David W. Golde

Mark R. Green

Jerome E. Groopman

William N. Halt

Adrian L. Harris

Curtis C. Harris

Sandra J. Horning

William J. Hoskins

Janet A. Houghton

Stephen B. Howell

Daniel C. lhde

John T. Isaacs

Robert B. Jenkins

David H. Johnson

V. Craig Jordan

Barton A. Kamen

Michael B. Kastan

Jeffrey M. Trent

Genetics, �

S. B. Kaye

David P. Kelsen

David Khayat

John M. Kirkwood

Donald W. Kufe

Steven M. Larson

John S. Lazo

Victor A. Levin

Allen Lichter

Marc E. Lippman

Edison T. Liu

Patrick J. Loehrer. Sr.

Dan L. Longo

Michael T. Lotze

Maurie Markman

William P. McGuire III

Roland Mertelsmann

Frank L. Meyskens, Jr.

John D. Minna

Monica Morrow

James L. Mulshine

Sharon B. Murphy

Charles E. Myers

Larry Norton

Richard J. O’Reilly

Robert F. Ozols

Ira Pastan

William P. Peters

Herbert M. Pinedo

Philip A. Pizzo

William K. Plunkett

Jerome B. Posner

Derek Raghavan

Mark J. Ratain

John C. Reed

Ralph A. Reisfeld

Jerome Ritz

Jack A. Roth

Eric B. Rowinsky

Edward A. Sausville

Howard I. Scher

Richard L. Schilsky

Richard M. Simon

John F. Smyth

Jeffrey A. Sosman

Michael B. Sporn

Louise C. Strong

Masaaki Terada

Daniel D. Von Hoff

Raymond P. Warrell. Jr.

Jane Weeks

Ralph R. Weichselbaum

Theresa L. Whiteside

Leonard A. Zwelhing

AACRPublications DepartmentPublic Ledger Building. Suite 826l5t) South Independence Mall WestPhiladelphia. PA 19106-3483Phone: (215) 440-93(XJ:FAX: (215) 440-9354

Clinical Cancer Research is published monthly. one volume per year. by the American Association tar Cancer Research. Inc. (AACR). Except tar menibers of the AACR. allsubscriptions are payabte in advance to Clinical Cancer Research. P.O. Box 3(XX). Denville. NJ t)7834 Telephone: (8(X)) 875-2997 or 21)1 � 627-2427: FAX: 201 � 627-55721. ii’ uhich allbusiness communications. remittances (in United States currency or its equivalent(. and subscription orders should be sent. in Japan. send orders and inquiries to sole agenic VSACOCorjxration. Tsutsurni Bldg.. 13-12. Shimba.shi 1-chonie. Minato-ku. Tokyo 105. Japan; Tel. (03( 502-6471. individuals who are not AACR nienihers ma� subscribe to Volume 3 ( t9�)7 ofClinical Cancer Research at the rate of $105 U.Si$l45 foreign. (‘linical fancer Research is onl� available to institutions as a combined subscription with Cancer Research. The combined1997 institutional subscription price of$685 U.SJ$815 tiweign includes 5l7() U.Si521() foreign for a subscription to ClinicalCancer Research. (Foreign subscription cost includes Cost of .urtacemail. For faster delivers. expedited mailing rates are available by contacting the AACR Publications Department.) Canadian subscribers should add 7i GST. Changes of address notifiCationshould be sent rt) days in advance and include both old and new addresses. Meniher subscribers should send address changes to: AACR Member Services. Public Ledger Bldg.. Suite 816. 1Sf)South Independence Mall West. Philadelphia. PA 19106-3483. Nonmember subscribers should send changes of address to: L’linical f�’ancer Research. P.O. Box 3)X�). Densitle. NJ ff7834.Copies of the journal which are undeliverable because of address changes will be destroyed. Through the kind assistance of the Japanese Cancer Association, accelerated mailing of alt AACRjournals to AACR members in Japan is supported by a generous grant from the Banyu Pharniaceutical Company. Tsukuba. Japan.

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Notice to Members of the American Association for Cancer Research

Officers fir 1997-1998

President: Donald S. Coffey, Johns Hopkins University School of Medicine, Baltimore, MD 21287-2101

President-Elect: Webster K. Cavenee, Ludwig Institute for Cancer Research, La Jolla, CA 92093-0660

Treasurer: Bayard D. Charkson, Memorial Sloan-Kettering Cancer Center, New York, NY 10021

E.vec’utii’e Director: Margaret Foti, AACR, Public Ledger Bldg., Suite 826, Philadelphia, PA 19 106-3483

Annual Dues

The annual dues of active members of the American Association for Cancer Research are $175, $50 of which may be applied to asubscription to Clinical c�amicer Research. Corresponding members of the Association will be charged an appropriate fee to offset

periodicals postage costs. Payment of dues and changes of address of members of the Association should be sent promptly toMargaret Foti, Executive Director, American Association for Cancer Research, Public Ledger Bldg., Suite 826, 150 SouthIndependence Mall West, Philadelphia, PA 19 106-3483; Telephone: (215) 440-9300: FAX: (215) 440-9313.

Submission of Manuscripts

Clinical Cancer Research, a journal of the American Associationfor Cancer Research, publishes original articles describing clinicalresearch on the cellular and molecular characterization, prevention,

diagnosis, and therapy of human cancer. Its focus is on innovative

clinical research and translational research which bridges the labo-ratory and the clinic. Clinical C’ancer Research is especially inter-

ested in clinical trials evaluating new treatments for cancer; researchon molecular abnormalities that predict incidence, response to ther-apy, and outcome; and laboratory studies of new drugs and biolog-ical agents that will lead to clinical trials in patients. All submissions

undergo peer review. Papers should be sent directly to an appropri-ate Senior Editor or to the Editor-in-Chief for review. See “Instruc-

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Cancer Research, Inc., since these articles are considered to be in

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The Journal will routinely allow authors (or others with the

permission of the authors) to include select parts of a copy-righted article in reviews, books. or subsequent papers, uponwritten request to the AACR Director of Publications. Requests

to reproduce an article in its entirety will be considered on anindividual basis and permission may be granted contingent upon

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No responsibility is accepted by the Editors, by the Amer-ican Association for Cancer Research, Inc., or by CadmusJournal Services for the opinions expressed by contributorsor for the content of the advertisements.

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Authors who wish to publish in Clinical Cancer Research mustformally transfer copyright to the proprietor of the journal. the

American Association for Cancer Research, Inc. It is under-stood by this transfer that the authors relinquish all exclusive

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Clinical Cancer Research is abstracted and/or indexed in Can-c’er Lit, Chemical Abstracts, and Current Comitents ( ClinicalMedicine).

Clinical Cancer Research (ISSN 1078-0432) is published monthlyby the American Association for Cancer Research, Inc., Public

Ledger Bldg., Suite 826, 150 South Independence Mall West,Philadelphia, PA l91()6-3483 for $50 annually for members and$ 105 for individual nonmembers. Clinical C’anc’er Research isonly available to institutions as a combined subscription with

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clinical c’ancer Research, P.O. Box 3000, Denville, NJ 07834.Copyright 1997 by the American Association for Cancer Re-search, Inc. Printed on acid-free paper in the U.S.A.

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AACR SPECIAL CONFERENCE IN CANCER RESEARCH

Co-Sponsored by the National Cancer Institute of Canada

Tumor Suppressor Genes

September 26-30, 1997Victoria Conference Centre

Victoria, BC, Canada

NATIONAL I INSTITUT NATIONALCANCER INSTITUTE I DU CANCEROF CANA� DU CANAIM

CONFERENCE CO-CHAIRPERSONS

Stephen H. Friend / Seattle, WA Philip Branton / Montreal, Quebec, Canada

CONFERENCE PROGRAM

p53 and ApoptosisSam Benchimol I Toronto, Ontario, CanadaMichael B. Kastan I Baltimore, MDCarol Prives I New York, NYScott W. Lowe I Cold Spring Harbor, NY

p21, p16, p27, and the CDK InhibitorsAnton J. M. Berns I Amsterdam, The

NetherlandsDenise A. Galloway I Seattle, WAGordon Peters I London, EnglandJames M. Roberts I Seattle, WA

RB/E2F/DP-1/p300/CBP

James A. DeCaprio I Boston, MABrenda L. Gallie 1 Toronto, Ontario, CanadaPaul A. Hamel I Toronto, Ontario, CanadaAmy S. Vee I Boston, MAElizabeth Moran I Philadelphia, PA

Functional Aspects of the E2F FamilyNicholas J. Dyson I Charlestown, MAKnstian Helm I Milan, ItalyJacqueline A. Lees I Cambridge, MAJoseph R. Nevins I Durham, NC

Tumor Suppressor Genes: From

Gene to FunctionWilliam G. Kaelin, Jr. I Boston, MAGordon Shore I Montreal, Quebec, Canada

Breast Cancer Susceptibility GenesTak W. Mak I Toronto, Ontario, CanadaElaine A. Ostrander I Seattle, WAFergus J. Couch I Philadelphia, PA

Therapeutic Implications of TumorSuppressor Genes and Late-Breaking NewsPhilip Branton I Montreal, Quebec, CanadaFrank P. McCormick I San Francisco, CAMichel Roberge I Vancouver, British Columbia, CanadaStephen H. Friend I Seattle, WA

Application Deadline: July 14, 1997

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Vol. 3, 1023, June 1997 Clinical Cancer Research 1023

AACR Bulletin Board

Institution of Page ChargesEffective January 1, 1997, a page charge of $35per printed page was levied on all manuscriptspublished in Clinical Cancer Research. It isunderstood at the time of submission that theauthor(s) agree to pay this charge in the eventof publication. Under exceptional circum-stances, when no other source of grant or othersupport exists, the author(s) may apply to Dr.Margaret Foti, Director of Publications, AACRPublications Department (see page ii for ad-dress) at the time of submission for a waiver ofthe page charges. All such applications must becountersigned by an appropriate institutionalofficial stating that no funds are available forthe payment of page charges.

Annual MeetingThe AACR’s Annual Meeting is one of thelargest and most important annual gather-ings of scientists engaged in cancer re-

search worldwide. The next Annual Meet-ing will take place in New Orleans, LA,March 28-April 1 , 1998. The Chairpersonof the Annual Meeting is Frank J. Rauscherifi of the Wistar Institute. The ProgramCommittee will invite outstanding scien-tists in the field to organize plenary ses-

sions, symposia, controversy sessions. and

meet-the-expert sunrise sessions. They alsolook forward to receiving for considerationfor presentation the proffered papers sub-milled by members of the cancer researchcommunity. All abstracts must be spon-sored by an AACR member in good stand-ing. The deadline for receipt of abstracts in

the AACR office will be October 28, 1997.

Call for Nominations for AACRAwardsThe Association presents six awards to dis-tinguished scientists at its Annual Meeting.The Awards Committee, consisting of sixseparate subsections, will recommend candi-dates for each award to the AACR ExecutiveCommittee. Below you will find a descrip-tion of each award. Members wishing tomake nominations should provide a shortdescription of the candidate’s accomplish-ments: the subcommittee involved will ob-tam further documentation on suitable con-didates. Nominations may be directed to theAssociation Office for forwarding to the ap-propriate subcommittee. This material shouldbe received no later than September 15,1997.

Clowes Memorial Award. The Eli LillyCompany established the Clowes MemorialLecture to honor Dr. G. H. A. Clowes, whowas a founding member of the AACR and aresearch director of Eli Lilly. The purpose ofthe award is to give “recognition of outstand-ing research accomplished in some recentperiod.” The Clowes Award should recog-nize outstanding recent accomplishments inbasic cancer research, and the Board of Di-rectors construes this to mean both labora-tory research and epidemiological investiga-tions.

Joseph H. Burchenal AACR ClinicalResearch Award. Bristol-Myers Squibb hasestablished this award to recognize outstand-ing achievements in clinical cancer research.It is named for Dr. Joseph H. Burchenal, past

AACRThe American Association for Cancer Re-search (AACR) was founded in 1907 to bringtogether active investigators of the cancerproblem for the presentation and discussionof new findings and to foster advances incancer research. Today the Association has13,000 members working in all of the sub-disciplines of cancer research in the UnitedStates, Canada, and more than 60 other coun-tries. Information on AACR programs andactivities can be obtained from

American Association forCancer Research

Public Ledger Building150 South Independence Mall West

Suite 826Philadelphia, PA 19106-3483

Phone: (215) 440-9300Fax: (215) 440-9313

E-mail: aacr@aacr.org

The AACR welcomes applications for mem-bership from the readership. Scientists en-gaged in all areas of cancer research areeligible for membership. There are three cat-egories of membership: active membership,open to cancer researchers working in theAmericas; corresponding membership, tothose working outside the Americas; and as-sociate membership. to graduate and medicalstudents, postdoctoral fellows, and physi-cians-in-training. Further information on thequalifications for each category as well as thebenefits of membership can be found on theapplication forms at the back of this issue.

president and honorary member of theAACR, and a leading figure in the field ofcancer chemotherapy. There are no restric-tions on the age or geographic location of theawardee.

Richard and Hinda Rosenthal Founda-tion Award. The Rosenthal Foundation hasestablished this award to “recognize re-search which has made or gives the prom-ise of soon making a notable contributionto improved clinical care in the field ofcancer.” The Foundation wishes to honorand provide incentive to young investiga-tors relatively early in their careers. It has,therefore, stipulated that the Associationrestrict the award to individuals who areengaged in the practice of medicine, whoreside in the Americas, and who will not bemore than 50 years of age at the time of theaward (March 1998).

Rhoads Memorial Award. In 1979, ananonymous donor established this award inmemory of Dr. Cornelius P. Rhoads, a foun-der and the first Director of the Sloan-Kettering Institute for Cancer Research. Thisannual award is intended to give recognitionto an “individual on the basis of meritoriousachievement in cancer research.” In accord-ance with the donor’s wishes, the awardeemust be a young investigator; therefore, theBoard of Directors of the Association hasstipulated that the recipient must not havereached his or her 41st birthday by the timeof the award (March 1998).

Cain Memorial Award. The Warner-Lambert Company instituted this award to

honor the memory of Dr. Bruce F. Cain ofNew Zealand for his work in the “design,synthesis, and biological evaluation of po-tential anticancer drugs.” The purpose ofthe award is to “give recognition to anindividual or research team for outstanding

preclinical research that has implicationsfor the improved care of cancer patients.”Examples of such research include discov-cry of a significant new anticancer agentand major contributions to a compound’sapplication as an antitumor agent. Theaward will recognize outstanding contribu-tions in the fields of medicinal chemistry,biochemistry, or tumor biology as relatedto drug discovery; will encompass antican-cer, antiviral, and antifungal agents; willhave no age limit: and will be internationalin scope.

American Cancer Society Award. TheAmerican Cancer Society sponsors thisaward to honor outstanding achievements inthe fields of epidemiology, biomarkers, andprevention. There arc no age or geographicalrestrictions on the awardee.

AACR Special Conferences in CancerResearch

A number of meetings are now beingorganized in the AACR’s series ofsmaller scientific meetings. Followingarc the topics, dates, locations, and pro-

gram committees for some of these meet-ings. When full details of each meeting

are available, AACR members will be thefirst to receive complete brochures and

application forms for participation inthese important conferences. Nonmem-bers may receive this information by

sending their names and addresses to

Meetings Mailing List, American Associa-tion for Cancer Research, Public LedgerBuilding, 150 South Independence MallWest, Suite 826, Philadelphia, PA 19106-3483. Telephone: (21 5) 440-9300. FAX:(215) 440-93 1 3. E-Mail: aacr@aacr.org.Up-to-date program information is avail-able via the Internet from the AACR’s web-site (http:llwww.aacr.org/ confrnc.html).

June 7-11, 1997Cancer of the Central Nervous System

Conference with Neurosurgery Joint Sec-

tion on Tutnors

Chairpersons:

PETER MeL. BLACK, Boston, MAWEBSTER K. CAVENEE, La Jolla, CALoews Coronado Bay Resort, SanDiego, CA

September 26-30, 1997Tumor Suppressor Genes

C’o-Sponsored by the National Cancer In-

stitute of Canada

Chairpersons:

PHILIP BRANTON, Montreal, Quebec,Canada

STEPHEN H. FRIEND, Seattle, WAVictoria Conference Centre, Victoria,BC, Canada