iv | CANCER DISCOVERY�OCTOBER 2013 www.aacrjournals.org

CANCERDISCOVERY CONTENTSOCTOBER 2013 ≠ VOLUME 3 ≠ NUMBER 10

In Focus

Connecting Genomic Alterations to Cancer Biology with Proteomics: The NCI Clinical Proteomic Tumor Analysis Consortium . . . . . . . . . . 1108M.J. Ellis, M. Gillette, S.A. Carr, A.G. Paulovich, R.D. Smith, K.K. Rodland, R.R. Townsend, C. Kinsinger, M. Mesri, H. Rodriguez, and D.C. Liebler

ceRNA Cross-Talk in Cancer: When ce-bling Rivalries Go Awry . . . . . . . . . . . . . 1113F.A. Karreth and P.P. Pandolfi

SF3B1 Mutations Are Associated with Alternative Splicing in Uveal Melanoma . . . . . . . . . . . . . 1122S.J. Furney, M. Pedersen, D. Gentien,A.G. Dumont, A. Rapinat, L. Desjardins,S. Turajlic, S. Piperno-Neumann, P. de la Grange, S. Roman-Roman, M.-H. Stern, and R. MaraisPrécis: Mutations in splicing factor 3b, subunit 1 (SF3B1) occur in approximately 15% of uveal melanomas and are associated with specifi c alternative splicing events.

Prostate Cancer Cell Telomere Length Variability and Stromal Cell Telomere Length as Prognostic Markers for Metastasis and Death . . . . . 1130C.M. Heaphy, G.S. Yoon, S.B. Peskoe, C.E. Joshu, T.K. Lee, E. Giovannucci, L.A. Mucci, S.A. Kenfi eld, M.J. Stampfer, J.L. Hicks, A.M. De Marzo, E.A. Platz, and A.K. MeekerPrécis: The combination of more variable telomere length among prostate cancer cells and shorter telomeres in cancer-associated stromal cells is associated with increased risk of tumor progression and death.

See commentary, p. 1096

MINI REVIEW

RESEARCHBRIEF

RESEARCHARTICLES

Highlighted research articles . . . . . . . . . . . . . . . . . . . . . . . .1083

Important news stories affecting the community . . . . . . . . . . . . . . . . . . . 1086

Q&A: Geoffrey Shapiro on Phase I Drug Trials . . . . . . . . 1089

Catch-22 for Cancer Tests . . . .1090

Selected highlights of recent articles of exceptional signifi cance from the cancer literature . . . . . . . . . . . . 1091

For more News and Research Watch, visit Cancer Discovery online at http://CDnews.aacrjournals.org.

In The Spotlight

Are Short Telomeres Predictive of Advanced Cancer? . . . . . . . . 1096J.W. Shay

See article, p. 1130

New Connections between Old Pathways: PDK1 Signaling Promotes Cellular Transformation through PLK1-Dependent MYC Stabilization . . . . . . . . . . . . . . . . . 1099J.T. Cunningham and D. Ruggero

See article, p. 1156

Hypoxia Signaling—License to Metastasize . . . . . . . . . . . . . . . 1103S. Vanharanta and J. Massagué

See article, p. 1190

Glycolysis Back in the Limelight: Systemic Targeting of HK2 Blocks Tumor Growth . . . . . . . . 1105S. Ros and A. Schulze

IN THIS ISSUE

NEWSIN BRIEF

NEWSIN DEPTH

RESEARCH WATCH

ONLINE

VIEWS

Research. on November 12, 2020. © 2013 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from

OCTOBER 2013�CANCER DISCOVERY | v

Bouwman and colleagues developed high-throughput functional comple-mentation assays to predict the pathogenicity of BRCA1 variants of un-known significance (VUS). BRCA1 VUSs were evaluated for their ability to rescue proliferation defects, cisplatin sensitivity, and olaparib sensitivity in murine embryonic stem cells lacking endogenous Brca1. The ability of BRCA1 VUSs to rescue growth defects and drug sensitivity correlated with their homologous recombination activity, indicating that these assays can predict BRCA1 functionality. Interestingly, all unambiguously predicted patho-genic BRCA1 variants were located in the RING and BRCT domains. This approach has the potential to rapidly characterize BRCA1 sequence variants identified dur-ing screening for germline mutations associated with increased risk of breast and ovarian cancer. For details, please see the article by Bouwman and colleagues on page 1142.

ON THE COVER

AC icon indicates Author ChoiceFor more information please visit http://www.aacrjournals.org

For more News and Research Watch, visit Cancer Discovery online at http://CDnews.aacrjournals.org. Online-only News stories include the following:

• For Adoptive T Cells, Setbacks and Success• Amgen to Buy Onyx for $10.4 Billion• Drug Firms Open Up on Trial Data Sharing

• AML Cells Block HSC Differentiation• Going Public on Cancer Stem Cells• A Boom in Clinical Genomics Services

A High-Throughput Functional Complementation Assay for Classifi cation of BRCA1 Missense Variants . . . . . . . . 1142P. Bouwman, H. van der Gulden, I. van der Heijden, R. Drost, C.N. Klijn, P. Prasetyanti, M. Pieterse,E. Wientjens, J. Seibler, F.B.L. Hogervorst, and J. JonkersPrécis: The pathogenicity of BRCA1 sequence variants of unknown signifi cance is determined based on their ability to rescue growth and DNA repair defects of Brca1-null cells.

PDK1 Signaling Toward PLK1–MYC Activation Confers Oncogenic Transformation, Tumor-Initiating Cell Activation, and Resistance to mTOR-Targeted Therapy . . . . . . . . . . . . . 1156J. Tan, Z. Li, P.L. Lee, P. Guan, M.Y. Aau, S.T. Lee, M. Feng, C.Z. Lim, E.Y.J. Lee, Z.N. Wee, Y.C. Lim, R.K.M. Karuturi, and Q. YuPrécis: A PDK1–PLK1–MYC signaling cascade promotes cancer cell growth and a cancer stem cell-like phenotype, and inhibition of PDK1/PLK1 is effective in MYC-dependent tumors.

See commentary, p. 1099

DEAR1 Is a Chromosome 1p35 Tumor Suppressor and Master Regulator of TGF-b–Driven Epithelial–Mesenchymal Transition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1172N. Chen, S. Balasenthil, J. Reuther, A. Frayna, Y. Wang, D.S. Chandler, L.V. Abruzzo, A. Rashid, J. Rodriguez, G. Lozano, Y. Cao, E. Lokken, J. Chen, M.L. Frazier, A.A. Sahin, I.I. Wistuba, S. Sen, S.T. Lott, and A. McNeill KillaryPrécis: Loss of DEAR1 drives tumor formation and enhances TGFβ-induced EMT and anoikis resistance via upregulation of SMAD3 signaling.

Hypoxia-Dependent Modifi cation of Collagen Networks Promotes Sarcoma Metastasis . . . . . . . . . . . . . . . . . 1190T.S.K. Eisinger-Mathason, M. Zhang, Q. Qiu, N. Skuli, M.S. Nakazawa, T. Karakasheva, V. Mucaj, J.E.S. Shay,L. Stangenberg, N. Sadri, E. Puré, S.S. Yoon, D.G. Kirsch, and M.C. SimonPrécis: Induction of the procollagen lysyl hydroxylase PLOD2 by HIF-1α alters extracellular collagen organization to facilitate migration and metastasis of sarcoma cells.

See commentary, p. 1103

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