Contents

Symposium Participants

Dedication

Foreword

Cancer Genetics and Genomes

Oncogenes Come of Age

H. Varmus, W. Pao, K. Politi, K. Podsypanina, and Y.–C.N. Du

Common and Contrasting Genomic Profiles among the Major Human Lung Cancer Subtypes

G. Tonon, C. Brennan, A. Protopopov, G. Maulik, B. Feng, Y. Zhang, D.B. Khatry, M.J. You, A.J. Aguirre, E.S. Martin, Z. Yang, H. Ji, L. Chin, K.–K. Wong, and R.A. DePinho

“Lineage Addiction” in Human Cancer: Lessons from Integrated Genomics

L.A. Garraway, B.A. Weir, X. Zhao, H. Widlund, R. Beroukhim, A. Berger, D. Rimm, M.A. Rubin, D.E. Fisher, M.L. Meyerson, and W.R. Sellers

Polygenic Inherited Predisposition to Breast Cancer

B.A.J. Ponder, A. Antoniou, A. Dunning, D.F. Easton, and P.D.P. Pharoah

Somatic Mutations in Human Cancer: Insights from Resequencing the Protein Kinase Gene Family

P.A. Futreal, R. Wooster, and M.R. Stratton

High–Resolution ROMA CGH and FISH Analysis of Aneuploid and Diploid Breast Tumors

J. Hicks, L. Muthuswamy, A. Krasnitz, N. Navin, M. Riggs, V. Grubor, D. Esposito, J. Alexander, J. Troge, M. Wigler, S. Maner, P. Lundin, and A. Zetterberg

Ductal Pancreatic Cancer in Humans and Mice

D.A. Tuveson and S.R. Hingorani

Detection of Oncogenic Mutations in the EGFR Gene in Lung Adenocarcinoma with Differential Sensitivity to EGFR Tyrosine Kinase Inhibitors

R.K. Thomas, H. Greulich, Y. Yuza, J.C. Lee, T. Tengs, W. Feng, T.–H. Chen, E. Nickerson, J. Simons, M. Egholm, J.M. Rothberg, W.R. Sellers, and M.L. Meyerson

Two Decades of Cancer Genetics: From Specificity to Pleiotropic Networks

S. Grisendi and P.P. Pandolfi

DNA Damage Response

Abnormalities of the Inactive X Chromosome Are a Common Feature of BRCA1 Mutant and Sporadic Basal–like Breast Cancer

S. Ganesan, A.L. Richardson, Z.C. Wang, J.D. Iglehart, A. Miron, J. Feunteun, D. Silver, and D.M. Livingston

The ATM–dependent DNA Damage Signaling Pathway

R. Kitagawa and M.B. Kastan

Single–Nucleotide Polymorphisms in the p53 Pathway

S.L. Harris, G. Gil, W. Hu, H. Robins, E. Bond, K. Hirshfield, Z. Feng, X. Yu, A.K. Teresky, G. Bond, and A.J. Levine

Transcriptional Regulation by p53 and p73

M. Lokshin, T. Tanaka, and C. Prives

p53–Dependent and –Independent Functions of the Arf Tumor Suppressor

C.J. Sherr, D. Bertwistle, W. den Besten, M.–L. Kuo, M. Sugimoto, K. Tago, R.T. Williams, F. Zindy, and M.F. Roussel

Exploiting the DNA Repair Defect in BRCA Mutant Cells in the Design of New Therapeutic Strategies for Cancer

A.N.J. Tutt, C.J. Lord, N. McCabe, H. Farmer, N. Turner, N.M. Martin, S.P. Jackson, G.C.M. Smith, and A. Ashworth

Cancer Biology and Stem Cells

Identifying Site–specific Metastasis Genes and Functions

G.P. Gupta, A.J. Minn, Y. Kang, P.M. Siegel, I. Serganova, C. Cordón–Cardo, A.B. Olshen, W.L. Gerald, and J. Massagué

The von Hippel–Lindau Tumor Suppressor Protein: Roles in Cancer and Oxygen Sensing

W.G. Kaelin, Jr.

The Src Substrate Tks5, Podosomes (Invadopodia), and Cancer Cell Invasion

S.A. Courtneidge, E.F. Azucena, Jr., I. Pass, D.F. Seals, and L. Tesfay

Modeling Neurofibromatosis Type 1 Tumors in the Mouse for Therapeutic Intervention

L.F. Parada, C.–H. Kwon, and Y. Zhu

Stem Cell Self–Renewal and Cancer Cell Proliferation Are Regulated by Common Networks That Balance the Activation of Proto–oncogenes and Tumor Suppressors

R. Pardal, A.V. Molofsky, S. He, and S.J. Morrison

Prostate Stem Cells and Prostate Cancer

D.A. Lawson, L. Xin, R. Lukacs, Q. Xu, D. Cheng, and O.N. Witte

Telomeres, Senescence, and Aging

Telomere–related Genome Instability in Cancer

T. de Lange

Telomerase and Cancer Stem Cells

M. Armanios and C.W. Greider

Regulation of Telomerase by Human Papillomaviruses

D.A. Galloway, L.C. Gewin, H. Myers, W. Luo, C. Grandori, R.A. Katzenellenbogen, and J.K. McDougall

Animal Models for Cancer

Genomic Progression in Mouse Models for Liver Tumors

A.D. Tward, K.D. Jones, S. Yant, M.A. Kay, R. Wang, and J.M. Bishop

Genotype–Phenotype Relationships in a Mouse Model for Human Small–Cell Lung Cancer

J. Calbó, R. Meuwissen, E. van Montfort, O. van Tellingen, and A. Berns

Cell Cycle and Cancer: Genetic Analysis of the Role of Cyclin–dependent Kinases

M. Barbacid, S. Ortega, R. Sotillo, J. Odajima, A. Martín, D. Santamaría, P. Dubus, and M. Malumbres

Mouse Models of Human Non–Small–Cell Lung Cancer: Raising the Bar

C.F.B. Kim, E.L. Jackson, D.G. Kirsch, J. Grimm, A.T. Shaw, K. Lane, J. Kissil, K.P. Olive, A. Sweet–Cordero, R. Weissleder, and T. Jacks

Generation and Analysis of Genetically Defined Liver Carcinomas Derived from Bipotential Liver Progenitors

L. Zender, W. Xue, C. Cordón–Cardo, G.J. Hannon, R. Lucito, S. Powers, P. Flemming, M.S. Spector, and S.W. Lowe

Oncogene–dependent Tumor Suppression: Using the Dark Side of the Force for Cancer Therapy

G.I. Evan, M. Christophorou, E.A. Lawlor, I. Ringshausen, J. Prescott, T. Dansen, A. Finch, C. Martins, and D. Murphy

Chromosomal Translocation Engineering to Recapitulate Primary Events of Human Cancer

A. Forster, R. Pannell, L. Drynan, F. Cano, N. Chan, R. Codrington, A. Daser, N. Lobato, M. Metzler, C.–H. Nam, S. Rodriguez, T. Tanaka, and T. Rabbitts

Deciphering Cancer Complexities in Genetically Engineered Mice

K. Simin, R. Hill, Y. Song, Q. Zhang, R. Bash, R.D. Cardiff, C. Yin, A. Xiao, K. McCarthy, and T. Van Dyke

Gene Expression and Cancer

The Evolving Portrait of Cancer Metastasis

P.B. Gupta, S. Mani, J. Yang, K. Hartwell, and R.A. Weinberg

Genomic Binding and Transcriptional Regulation by the Drosophila Myc and Mnt Transcription Factors

A. Orian, S.S. Grewal, P.S. Knoepfler, B.A. Edgar, S.M. Parkhurst, and R.N. Eisenman

Regulation of the Arf/p53 Tumor Surveillance Network by E2F

P.J. Iaquinta, A. Aslanian, and J.A. Lees

Genetic and Epigenetic Changes in Mammary Epithelial Cells Identify a Subpopulation of Cells Involved in Early Carcinogenesis

H. Berman, J. Zhang, Y.G. Crawford, M.L. Gauthier, C.A. Fordyce, K. McDermott, M. Sigaroudinia, K. Kozakiewicz, and T.D. Tlsty

Epigenetic Changes in Cancer and Preneoplasia

J.G. Herman

A Genetic Approach to Cancer Epigenetics

A.P. Feinberg

Tumor Responses to Microenvironment

Microenvironmental Regulators of Tissue Structure and Function Also Regulate Tumor Induction and Progression: The Role of Extracellular Matrix and Its Degrading Enzymes

M.J. Bissell, P.A. Kenny, and D.C. Radisky

How Do Cancer Cells Acquire the Fuel Needed to Support Cell Growth?

C.B. Thompson, D.E. Bauer, J.J. Lum, G. Hatzivassiliou, W.–X. Zong, D. Ditsworth, F. Zhao, M. Buzzai, and T. Lindsten

Mitochondria and Cancer: Warburg Addressed

D.C. Wallace

Inductions of Complete Regressions of Oncogene–induced Breast Tumors in Mice

R. Benezra, E. Henke, A. Ciarrocchi, M. Ruzinova, D. Solit, N. Rosen, D. Nolan, V. Mittal, and P. de Candia

The Fibroblastic Coconspirator in Cancer Progression

M. Egeblad, L.E. Littlepage, and Z. Werb

Angiogenesis

Is Oncogene Addiction Angiogenesis–dependent?

J. Folkman and S. Ryeom

Structural Basis for the Functions of Endogenous Angiogenesis Inhibitors

M.A. Grant and R. Kalluri

VEGF Trap as a Novel Antiangiogenic Treatment Currently in Clinical Trials for Cancer and Eye Diseases, and VelociGene–based Discovery of the Next Generation of Angiogenesis Targets

J.S. Rudge, G. Thurston, S. Davis, N. Papadopoulos, N. Gale, S.J. Wiegand, and G.D. Yancopoulos

Discovering Cancer Targets

Molecular Targeted Therapy of Lung Cancer: EGFR Mutations and Response to EGFR Inhibitors

D.A. Haber, D.W. Bell, R. Sordella, E.L. Kwak, N. Godin–Heymann, S.V. Sharma, T.J. Lynch, and J. Settleman

Aberrant Gene Silencing in Tumor Progression: Implications for Control of Cancer

S.B. Baylin and W.Y. Chen

Dissecting Cancer Pathways and Vulnerabilities with RNAi

T.F. Westbrook, F. Stegmeier, and S.J. Elledge

Emerging Approaches in Molecular Profiling Affecting Oncology Drug Discovery

S.H. Friend

Screens Using RNAi and cDNA Expression as Surrogates for Genetics in Mammalian Tissue Culture Cells

J. Pearlberg, S. Degot, W. Endege, J. Park, J. Davies, E. Gelfand, J. Sawyer, A. Conery, J. Doench, W. Li, L. Gonzalez, F.M. Boyce, L. Brizuela, J. LaBaer, D. Grueneberg, and E. Harlow

Cancer Targets in the Ras Pathway

P. Rodriguez–Viciana, O. Tetsu, K. Oda, J. Okada, K. Rauen, and F. McCormick

Author Index

Subject Index