Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 321 (5897): 1801-1806

Copyright © 2008 by the American Association for the Advancement of Science

Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses

Siân Jones,1* Xiaosong Zhang,1* D. Williams Parsons,1,2* Jimmy Cheng-Ho Lin,1* Rebecca J. Leary,1* Philipp Angenendt,1* Parminder Mankoo,3 Hannah Carter,3 Hirohiko Kamiyama,4 Antonio Jimeno,1 Seung-Mo Hong,4 Baojin Fu,4 Ming-Tseh Lin,4 Eric S. Calhoun,1 Mihoko Kamiyama,4 Kimberly Walter,4 Tatiana Nikolskaya,5 Yuri Nikolsky,6 James Hartigan,7 Douglas R. Smith,7 Manuel Hidalgo,1 Steven D. Leach,1,8 Alison P. Klein,1,4 Elizabeth M. Jaffee,1,4 Michael Goggins,1,4 Anirban Maitra,1,4 Christine Iacobuzio-Donahue,1,4 James R. Eshleman,1,4 Scott E. Kern,1,4 Ralph H. Hruban,1,4 Rachel Karchin,3 Nickolas Papadopoulos,1 Giovanni Parmigiani,1,9 Bert Vogelstein,1{dagger} Victor E. Velculescu,1{dagger} Kenneth W. Kinzler1{dagger}

Abstract: There are currently few therapeutic options for patients with pancreatic cancer, and new insights into the pathogenesis of this lethal disease are urgently needed. Toward this end, we performed a comprehensive genetic analysis of 24 pancreatic cancers. We first determined the sequences of 23,219 transcripts, representing 20,661 protein-coding genes, in these samples. Then, we searched for homozygous deletions and amplifications in the tumor DNA by using microarrays containing probes for ~106 single-nucleotide polymorphisms. We found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations. These alterations defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors. Analysis of these tumors' transcriptomes with next-generation sequencing-by-synthesis technologies provided independent evidence for the importance of these pathways and processes. Our data indicate that genetically altered core pathways and regulatory processes only become evident once the coding regions of the genome are analyzed in depth. Dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis.

1 Sol Goldman Pancreatic Cancer Research Center, Ludwig Center and Howard Hughes Medical Institute at the Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.
2 Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX 77030, USA.
3 Department of Biomedical Engineering, Institute of Computational Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21218, USA.
4 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
5 Vavilov Institute for General Genetics, Moscow B333, 117809, Russia.
6 GeneGo, Incorporated, St. Joseph, MI 49085, USA.
7 Agencourt Bioscience Corporation, Beverly, MA 01915, USA.
8 Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
9 Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: bertvog{at}gmail.com (B.V.); velculescu{at}jhmi.edu (V.E.V.); kinzlke{at}jhmi.edu (K.W.K.)

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Genomics-Driven Oncology: Framework for an Emerging Paradigm.
L. A. Garraway (2013)
J. Clin. Oncol. 31, 1806-1814
   Abstract »    Full Text »    PDF »
Personalizing Oncology: Perspectives and Prospects.
J. Mendelsohn (2013)
J. Clin. Oncol. 31, 1904-1911
   Abstract »    Full Text »    PDF »
Systematic tracking of dysregulated modules identifies novel genes in cancer.
S. Srihari and M. A. Ragan (2013)
Bioinformatics
   Abstract »    Full Text »    PDF »
Expression quantitative trait loci: present and future.
A. C. Nica and E. T. Dermitzakis (2013)
Phil Trans R Soc B 368, 20120362
   Abstract »    Full Text »    PDF »
Evolving Panorama of Treatment for Metastatic Pancreas Adenocarcinoma.
E. M. O'Reilly (2013)
J. Clin. Oncol. 31, 1621-1623
   Full Text »    PDF »
Identification of cancer fusion drivers using network fusion centrality.
C.-C. Wu, K. Kannan, S. Lin, L. Yen, and A. Milosavljevic (2013)
Bioinformatics 29, 1174-1181
   Abstract »    Full Text »    PDF »
Cancer Genome Landscapes.
B. Vogelstein, N. Papadopoulos, V. E. Velculescu, S. Zhou, L. A. Diaz Jr., and K. W. Kinzler (2013)
Science 339, 1546-1558
   Abstract »    Full Text »    PDF »
Kinesin-1 and mitochondrial motility control by discrimination of structurally equivalent but distinct subdomains in Ran-GTP-binding domains of Ran-binding protein 2.
H. Patil, K.-i. Cho, J. Lee, Y. Yang, A. Orry, and P. A. Ferreira (2013)
Open Bio 3, 120183
   Abstract »    Full Text »    PDF »
Dormant Cancer Cells Contribute to Residual Disease in a Model of Reversible Pancreatic Cancer.
W.-c. Lin, N. Rajbhandari, C. Liu, K. Sakamoto, Q. Zhang, A. A. Triplett, S. K. Batra, R. Opavsky, D. W. Felsher, D. J. DiMaio, et al. (2013)
Cancer Res. 73, 1821-1830
   Abstract »    Full Text »    PDF »
Identification of molecular alterations in gastrointestinal carcinomas and dysplastic hamartomas in Peutz-Jeghers syndrome.
S. E. Korsse, K. Biermann, G. J. A. Offerhaus, A. Wagner, E. Dekker, E. M. H. Mathus-Vliegen, E. J. Kuipers, M. E. van Leerdam, and W. van Veelen (2013)
Carcinogenesis
   Abstract »    Full Text »    PDF »
Personalized Chemotherapy Profiling Using Cancer Cell Lines from Selectable Mice.
H. Kamiyama, S. Rauenzahn, J. S. Shim, C. A. Karikari, G. Feldmann, L. Hua, M. Kamiyama, F. W. Schuler, M.-T. Lin, R. M. Beaty, et al. (2013)
Clin. Cancer Res. 19, 1139-1146
   Abstract »    Full Text »    PDF »
CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia.
M. E. McNerney, C. D. Brown, X. Wang, E. T. Bartom, S. Karmakar, C. Bandlamudi, S. Yu, J. Ko, B. P. Sandall, T. Stricker, et al. (2013)
Blood 121, 975-983
   Abstract »    Full Text »    PDF »
Exomic Sequencing of Medullary Thyroid Cancer Reveals Dominant and Mutually Exclusive Oncogenic Mutations in RET and RAS.
N. Agrawal, Y. Jiao, M. Sausen, R. Leary, C. Bettegowda, N. J. Roberts, S. Bhan, A. S. Ho, Z. Khan, J. Bishop, et al. (2013)
J. Clin. Endocrinol. Metab. 98, E364-E369
   Abstract »    Full Text »    PDF »
Current concepts and novel targets in advanced pancreatic cancer.
P. Michl and T. M. Gress (2013)
Gut 62, 317-326
   Abstract »    Full Text »    PDF »
SMAD2, SMAD3 and SMAD4 Mutations in Colorectal Cancer.
N. I. Fleming, R. N. Jorissen, D. Mouradov, M. Christie, A. Sakthianandeswaren, M. Palmieri, F. Day, S. Li, C. Tsui, L. Lipton, et al. (2013)
Cancer Res. 73, 725-735
   Abstract »    Full Text »    PDF »
Oxidants, antioxidants and the current incurability of metastatic cancers.
J. Watson (2013)
Open Bio 3, 120144
   Abstract »    Full Text »    PDF »
A Universally Conserved ATPase Regulates the Oxidative Stress Response in Escherichia coli.
M. Wenk, Q. Ba, V. Erichsen, K. MacInnes, H. Wiese, B. Warscheid, and H.-G. Koch (2012)
J. Biol. Chem. 287, 43585-43598
   Abstract »    Full Text »    PDF »
Genetically Defined Subsets of Human Pancreatic Cancer Show Unique In Vitro Chemosensitivity.
Y. Cui, J. A. Brosnan, A. L. Blackford, S. Sur, R. H. Hruban, K. W. Kinzler, B. Vogelstein, A. Maitra, L. A. Diaz Jr, C. A. Iacobuzio-Donahue, et al. (2012)
Clin. Cancer Res. 18, 6519-6530
   Abstract »    Full Text »    PDF »
A novel missense-mutation-related feature extraction scheme for 'driver' mutation identification.
H. Tan, J. Bao, and X. Zhou (2012)
Bioinformatics 28, 2948-2955
   Abstract »    Full Text »    PDF »
Efficient methods for identifying mutated driver pathways in cancer.
J. Zhao, S. Zhang, L.-Y. Wu, and X.-S. Zhang (2012)
Bioinformatics 28, 2940-2947
   Abstract »    Full Text »    PDF »
Accelerating Cancer Therapy Development: The Importance of Combination Strategies and Collaboration. Summary of an Institute of Medicine Workshop.
P. M. LoRusso, R. Canetta, J. A. Wagner, E. P. Balogh, S. J. Nass, S. A. Boerner, and J. Hohneker (2012)
Clin. Cancer Res. 18, 6101-6109
   Abstract »    Full Text »    PDF »
Clinical Significance of the Genetic Landscape of Pancreatic Cancer and Implications for Identification of Potential Long-term Survivors.
S. Yachida, C. M. White, Y. Naito, Y. Zhong, J. A. Brosnan, A. M. Macgregor-Das, R. A. Morgan, T. Saunders, D. A. Laheru, J. M. Herman, et al. (2012)
Clin. Cancer Res. 18, 6339-6347
   Abstract »    Full Text »    PDF »
The Kelch Protein KLHDC8B Guards against Mitotic Errors, Centrosomal Amplification, and Chromosomal Instability.
M. M. Krem, P. Luo, B. I. Ing, and M. S. Horwitz (2012)
J. Biol. Chem. 287, 39083-39093
   Abstract »    Full Text »    PDF »
Wnt Antagonist SFRP1 Functions as a Secreted Mediator of Senescence.
D. J. Elzi, M. Song, K. Hakala, S. T. Weintraub, and Y. Shiio (2012)
Mol. Cell. Biol. 32, 4388-4399
   Abstract »    Full Text »    PDF »
A Preclinical Evaluation of Minnelide as a Therapeutic Agent Against Pancreatic Cancer.
R. Chugh, V. Sangwan, S. P. Patil, V. Dudeja, R. K. Dawra, S. Banerjee, R. J. Schumacher, B. R. Blazar, G. I. Georg, S. M. Vickers, et al. (2012)
Science Translational Medicine 4, 156ra139
   Abstract »    Full Text »    PDF »
Genetically engineered mouse models of pancreatic cancer: unravelling tumour biology and progressing translational oncology.
P. K. Mazur and J. T. Siveke (2012)
Gut 61, 1488-1500
   Abstract »    Full Text »    PDF »
Diversity of Antigen-Specific Responses Induced In Vivo with CTLA-4 Blockade in Prostate Cancer Patients.
S. S. Kwek, V. Dao, R. Roy, Y. Hou, D. Alajajian, J. P. Simko, E. J. Small, and L. Fong (2012)
J. Immunol. 189, 3759-3766
   Abstract »    Full Text »    PDF »
Sialofucosylated podocalyxin is a functional E- and L-selectin ligand expressed by metastatic pancreatic cancer cells.
M. R. Dallas, S.-H. Chen, M. M. Streppel, S. Sharma, A. Maitra, and K. Konstantopoulos (2012)
Am J Physiol Cell Physiol 303, C616-C624
   Abstract »    Full Text »    PDF »
Efficient sampling for Bayesian inference of conjunctive Bayesian networks.
T. Sakoparnig and N. Beerenwinkel (2012)
Bioinformatics 28, 2318-2324
   Abstract »    Full Text »    PDF »
Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma.
J. B. Bachet, R. Marechal, P. Demetter, F. Bonnetain, A. Couvelard, M. Svrcek, A. Bardier-Dupas, P. Hammel, A. Sauvanet, C. Louvet, et al. (2012)
Ann. Onc. 23, 2327-2335
   Abstract »    Full Text »    PDF »
Interplay between Smoking-induced Genotoxicity and Altered Signaling in Pancreatic Carcinogenesis.
N. Momi, S. Kaur, M. P. Ponnusamy, S. Kumar, U. A. Wittel, and S. K. Batra (2012)
Carcinogenesis 33, 1617-1628
   Abstract »    Full Text »    PDF »
Exome sequencing identifies MXRA5 as a novel cancer gene frequently mutated in non-small cell lung carcinoma from Chinese patients.
D. Xiong, G. Li, K. Li, Q. Xu, Z. Pan, F. Ding, P. Vedell, P. Liu, P. Cui, X. Hua, et al. (2012)
Carcinogenesis 33, 1797-1805
   Abstract »    Full Text »    PDF »
The Gamma Secretase Inhibitor MRK-003 Attenuates Pancreatic Cancer Growth in Preclinical Models.
M. Mizuma, Z. A. Rasheed, S. Yabuuchi, N. Omura, N. R. Campbell, R. F. de Wilde, E. De Oliveira, Q. Zhang, O. Puig, W. Matsui, et al. (2012)
Mol. Cancer Ther. 11, 1999-2009
   Abstract »    Full Text »    PDF »
Evolution of the Voltage Sensor Domain of the Voltage-Sensitive Phosphoinositide Phosphatase VSP/TPTE Suggests a Role as a Proton Channel in Eutherian Mammals.
K. A. Sutton, M. K. Jungnickel, L. Jovine, and H. M. Florman (2012)
Mol. Biol. Evol. 29, 2147-2155
   Abstract »    Full Text »    PDF »
New insights into pancreatic cancer biology.
M. Hidalgo (2012)
Ann. Onc. 23, x135-x138
   Abstract »    Full Text »    PDF »
Translational Therapeutic Opportunities in Ductal Adenocarcinoma of the Pancreas.
M. Hidalgo and D. D. Von Hoff (2012)
Clin. Cancer Res. 18, 4249-4256
   Abstract »    Full Text »    PDF »
Genetic Basis of Pancreas Cancer Development and Progression: Insights from Whole-Exome and Whole-Genome Sequencing.
C. A. Iacobuzio-Donahue, V. E. Velculescu, C. L. Wolfgang, and R. H. Hruban (2012)
Clin. Cancer Res. 18, 4257-4265
   Abstract »    Full Text »    PDF »
Heterogeneity and Targeting of Pancreatic Cancer Stem Cells.
V. R. Penchev, Z. A. Rasheed, A. Maitra, and W. Matsui (2012)
Clin. Cancer Res. 18, 4277-4284
   Abstract »    Full Text »    PDF »
Genome-Wide Somatic Copy Number Alterations in Low-Grade PanINs and IPMNs from Individuals with a Family History of Pancreatic Cancer.
S.-M. Hong, A. Vincent, M. Kanda, J. Leclerc, N. Omura, M. Borges, A. P. Klein, M. I. Canto, R. H. Hruban, and M. Goggins (2012)
Clin. Cancer Res. 18, 4303-4312
   Abstract »    Full Text »    PDF »
International Cancer Genome Consortium Data Portal--a one-stop shop for cancer genomics data.
J. Zhang, J. Baran, A. Cros, J. M. Guberman, S. Haider, J. Hsu, Y. Liang, E. Rivkin, J. Wang, B. Whitty, et al. (2012)
Database 2011, bar026
   Abstract »    Full Text »    PDF »
Phosphoproteomic Analysis of Leukemia Cells under Basal and Drug-treated Conditions Identifies Markers of Kinase Pathway Activation and Mechanisms of Resistance.
M. P. Alcolea, P. Casado, J.-C. Rodriguez-Prados, B. Vanhaesebroeck, and P. R. Cutillas (2012)
Mol. Cell. Proteomics 11, 453-466
   Abstract »    Full Text »    PDF »
Preservation of HUGL-1 Expression as a Favourable Prognostic Factor in Pancreatic Carcinoma.
S. BIESTERFELD, A. KAUHAUSEN, C. KOST, I. GOCKEL, C. C. SCHIMANSKI, and P. R. GALLE (2012)
Anticancer Res 32, 3153-3159
   Abstract »    Full Text »    PDF »
Molecular Mechanisms Involved in the Synergistic Interaction of the EZH2 Inhibitor 3-Deazaneplanocin A with Gemcitabine in Pancreatic Cancer Cells.
A. Avan, F. Crea, E. Paolicchi, N. Funel, E. Galvani, V. E. Marquez, R. J. Honeywell, R. Danesi, G. J. Peters, and E. Giovannetti (2012)
Mol. Cancer Ther. 11, 1735-1746
   Abstract »    Full Text »    PDF »
The Utility of Hedgehog Signaling Pathway Inhibition for Cancer.
S. Sahebjam, L. L. Siu, and A. A. Razak (2012)
Oncologist 17, 1090-1099
   Abstract »    Full Text »    PDF »
Transforming Growth Factor {beta} Inhibits Bone Morphogenetic Protein-Induced Transcription through Novel Phosphorylated Smad1/5-Smad3 Complexes.
E. Gronroos, I. J. Kingston, A. Ramachandran, R. A. Randall, P. Vizan, and C. S. Hill (2012)
Mol. Cell. Biol. 32, 2904-2916
   Abstract »    Full Text »    PDF »
A Replication Study and Genome-Wide Scan of Single-Nucleotide Polymorphisms Associated with Pancreatic Cancer Risk and Overall Survival.
J. A. Willis, S. H. Olson, I. Orlow, S. Mukherjee, R. R. McWilliams, R. C. Kurtz, and R. J. Klein (2012)
Clin. Cancer Res. 18, 3942-3951
   Abstract »    Full Text »    PDF »
Reproducible Quantification of Cancer-Associated Proteins in Body Fluids Using Targeted Proteomics.
R. Huttenhain, M. Soste, N. Selevsek, H. Rost, A. Sethi, C. Carapito, T. Farrah, E. W. Deutsch, U. Kusebauch, R. L. Moritz, et al. (2012)
Science Translational Medicine 4, 142ra94
   Abstract »    Full Text »    PDF »
A systematic approach to therapeutic target selection in oesophago-gastric cancer.
A. L. Paterson, N. B. Shannon, P. Lao-Sirieix, C.-A. J. Ong, C. J. Peters, M. O'Donovan, and R. C. Fitzgerald (2012)
Gut
   Abstract »    Full Text »
Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer.
D. Li, E. J. Duell, K. Yu, H. A. Risch, S. H. Olson, C. Kooperberg, B. M. Wolpin, L. Jiao, X. Dong, B. Wheeler, et al. (2012)
Carcinogenesis 33, 1384-1390
   Abstract »    Full Text »    PDF »
Genetic evolution of pancreatic cancer: lessons learnt from the pancreatic cancer genome sequencing project.
C. A. Iacobuzio-Donahue (2012)
Gut 61, 1085-1094
   Abstract »    Full Text »    PDF »
Joint Bayesian inference of condition-specific miRNA and transcription factor activities from combined gene and microRNA expression data.
B. Zacher, K. Abnaof, S. Gade, E. Younesi, A. Tresch, and H. Frohlich (2012)
Bioinformatics 28, 1714-1720
   Abstract »    Full Text »    PDF »
A Sleeping Beauty mutagenesis screen reveals a tumor suppressor role for Ncoa2/Src-2 in liver cancer.
K. A. O'Donnell, V. W. Keng, B. York, E. L. Reineke, D. Seo, D. Fan, K. A. T. Silverstein, C. T. Schrum, W. R. Xie, L. Mularoni, et al. (2012)
PNAS 109, E1377-E1386
   Abstract »    Full Text »    PDF »
GLP-1 Receptor Agonist Effects on Normal and Neoplastic Pancreata.
M. Goggins (2012)
Diabetes 61, 989-990
   Full Text »    PDF »
PTMScan Direct: Identification and Quantification of Peptides from Critical Signaling Proteins by Immunoaffinity Enrichment Coupled with LC-MS/MS.
M. P. Stokes, C. L. Farnsworth, A. Moritz, J. C. Silva, X. Jia, K. A. Lee, A. Guo, R. D. Polakiewicz, and M. J. Comb (2012)
Mol. Cell. Proteomics 11, 187-201
   Abstract »    Full Text »    PDF »
Oncogenomics Methods and Resources.
S. J. Furney, G. Gundem, and N. Lopez-Bigas (2012)
Cold Spring Harb Protoc 2012, pdb.top069229
   Abstract »    Full Text »    PDF »
The activity of Gli transcription factors is essential for Kras-induced pancreatic tumorigenesis.
M. Rajurkar, W. E. De Jesus-Monge, D. R. Driscoll, V. A. Appleman, H. Huang, J. L. Cotton, D. S. Klimstra, L. J. Zhu, K. Simin, L. Xu, et al. (2012)
PNAS 109, E1038-E1047
   Abstract »    Full Text »    PDF »
Sleeping Beauty mutagenesis reveals cooperating mutations and pathways in pancreatic adenocarcinoma.
K. M. Mann, J. M. Ward, C. C. K. Yew, A. Kovochich, D. W. Dawson, M. A. Black, B. T. Brett, T. E. Sheetz, A. J. Dupuy, Australian Pancreatic Cancer Genome Initiative, et al. (2012)
PNAS 109, 5934-5941
   Abstract »    Full Text »    PDF »
The RalB Small GTPase Mediates Formation of Invadopodia through a GTPase-Activating Protein-Independent Function of the RalBP1/RLIP76 Effector.
N. F. Neel, K. L. Rossman, T. D. Martin, T. K. Hayes, J. J. Yeh, and C. J. Der (2012)
Mol. Cell. Biol. 32, 1374-1386
   Abstract »    Full Text »    PDF »
Phase I Study of Rigosertib, an Inhibitor of the Phosphatidylinositol 3-Kinase and Polo-like Kinase 1 Pathways, Combined with Gemcitabine in Patients with Solid Tumors and Pancreatic Cancer.
W. W. Ma, W. A. Messersmith, G. K. Dy, C. D. Weekes, A. Whitworth, C. Ren, M. Maniar, F. Wilhelm, S. G. Eckhardt, A. A. Adjei, et al. (2012)
Clin. Cancer Res. 18, 2048-2055
   Abstract »    Full Text »    PDF »
Leveling the Playing Field: Bringing Development of Biomarkers and Molecular Diagnostics up to the Standards for Drug Development.
G. Poste, D. P. Carbone, D. R. Parkinson, J. Verweij, S. M. Hewitt, and J. M. Jessup (2012)
Clin. Cancer Res. 18, 1515-1523
   Abstract »    Full Text »    PDF »
Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma.
N. Cook, K. K. Frese, T. E. Bapiro, M. A. Jacobetz, A. Gopinathan, J. L. Miller, S. S. Rao, T. Demuth, W. J. Howat, D. I. Jodrell, et al. (2012)
J. Exp. Med. 209, 437-444
   Abstract »    Full Text »    PDF »
New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel.
J.- L. Van Laethem, C. Verslype, J. L. Iovanna, P. Michl, T. Conroy, C. Louvet, P. Hammel, E. Mitry, M. Ducreux, T. Maraculla, et al. (2012)
Ann. Onc. 23, 570-576
   Abstract »    Full Text »    PDF »
Pancreatic ductal adenocarcinoma and acinar cells: a matter of differentiation and development?.
I. Rooman and F. X. Real (2012)
Gut 61, 449-458
   Abstract »    Full Text »    PDF »
Mucin 16 is a functional selectin ligand on pancreatic cancer cells.
S.-H. Chen, M. R. Dallas, E. M. Balzer, and K. Konstantopoulos (2012)
FASEB J 26, 1349-1359
   Abstract »    Full Text »    PDF »
Integrative Survival-Based Molecular Profiling of Human Pancreatic Cancer.
T. R. Donahue, L. M. Tran, R. Hill, Y. Li, A. Kovochich, J. H. Calvopina, S. G. Patel, N. Wu, A. Hindoyan, J. J. Farrell, et al. (2012)
Clin. Cancer Res. 18, 1352-1363
   Abstract »    Full Text »    PDF »
Cancer Genomics: Technology, Discovery, and Translation.
B. Tran, J. E. Dancey, S. Kamel-Reid, J. D. McPherson, P. L. Bedard, A. M. K. Brown, T. Zhang, P. Shaw, N. Onetto, L. Stein, et al. (2012)
J. Clin. Oncol. 30, 647-660
   Abstract »    Full Text »    PDF »
Unique DNA methylome profiles in CpG island methylator phenotype colon cancers.
Y. Xu, B. Hu, A.-J. Choi, B. Gopalan, B. H. Lee, M. F. Kalady, J. M. Church, and A. H. Ting (2012)
Genome Res. 22, 283-291
   Abstract »    Full Text »    PDF »
Whole-exome sequencing of human pancreatic cancers and characterization of genomic instability caused by MLH1 haploinsufficiency and complete deficiency.
L. Wang, S. Tsutsumi, T. Kawaguchi, K. Nagasaki, K. Tatsuno, S. Yamamoto, F. Sang, K. Sonoda, M. Sugawara, A. Saiura, et al. (2012)
Genome Res. 22, 208-219
   Abstract »    Full Text »    PDF »
De novo discovery of mutated driver pathways in cancer.
F. Vandin, E. Upfal, and B. J. Raphael (2012)
Genome Res. 22, 375-385
   Abstract »    Full Text »    PDF »
Primary Colorectal Cancers and Their Subsequent Hepatic Metastases Are Genetically Different: Implications for Selection of Patients for Targeted Treatment.
J. S. Vermaat, I. J. Nijman, M. J. Koudijs, F. L. Gerritse, S. J. Scherer, M. Mokry, W. M. Roessingh, N. Lansu, E. de Bruijn, R. van Hillegersberg, et al. (2012)
Clin. Cancer Res. 18, 688-699
   Abstract »    Full Text »    PDF »
Genome-Wide CpG Island Profiling of Intraductal Papillary Mucinous Neoplasms of the Pancreas.
S.-M. Hong, N. Omura, A. Vincent, A. Li, S. Knight, J. Yu, R. H. Hruban, and M. Goggins (2012)
Clin. Cancer Res. 18, 700-712
   Abstract »    Full Text »    PDF »
Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer.
A. H. Shain, C. P. Giacomini, K. Matsukuma, C. A. Karikari, M. D. Bashyam, M. Hidalgo, A. Maitra, and J. R. Pollack (2012)
PNAS 109, E252-E259
   Abstract »    Full Text »    PDF »
A SUMOylation-Dependent Transcriptional Subprogram Is Required for Myc-Driven Tumorigenesis.
J. D. Kessler, K. T. Kahle, T. Sun, K. L. Meerbrey, M. R. Schlabach, E. M. Schmitt, S. O. Skinner, Q. Xu, M. Z. Li, Z. C. Hartman, et al. (2012)
Science 335, 348-353
   Abstract »    Full Text »    PDF »
EpCAM/CD3-Bispecific T-cell Engaging Antibody MT110 Eliminates Primary Human Pancreatic Cancer Stem Cells.
M. Cioffi, J. Dorado, P. A. Baeuerle, and C. Heeschen (2012)
Clin. Cancer Res. 18, 465-474
   Abstract »    Full Text »    PDF »
Loss of 18q22.3 Involving the Carboxypeptidase of Glutamate-like Gene Is Associated with Poor Prognosis in Resected Pancreatic Cancer.
J.-H. Lee, E. Giovannetti, J.-H. Hwang, I. Petrini, Q. Wang, J. Voortman, Y. Wang, S. M. Steinberg, N. Funel, P. S. Meltzer, et al. (2012)
Clin. Cancer Res. 18, 524-533
   Abstract »    Full Text »    PDF »
Network of Cancer Genes (NCG 3.0): integration and analysis of genetic and network properties of cancer genes.
M. D'Antonio, V. Pendino, S. Sinha, and F. D. Ciccarelli (2012)
Nucleic Acids Res. 40, D978-D983
   Abstract »    Full Text »    PDF »
GLI1 Inhibition Promotes Epithelial-to-Mesenchymal Transition in Pancreatic Cancer Cells.
S. Joost, L. L. Almada, V. Rohnalter, P. S. Holz, A. M. Vrabel, M. G. Fernandez-Barrena, R. R. McWilliams, M. Krause, M. E. Fernandez-Zapico, and M. Lauth (2012)
Cancer Res. 72, 88-99
   Abstract »    Full Text »    PDF »
Pancreatic endocrine tumours: mutational and immunohistochemical survey of protein kinases reveals alterations in targetable kinases in cancer cell lines and rare primaries.
V. Corbo, S. Beghelli, S. Bersani, D. Antonello, G. Talamini, M. Brunelli, P. Capelli, M. Falconi, and A. Scarpa (2012)
Ann. Onc. 23, 127-134
   Abstract »    Full Text »    PDF »
Molecular Determinants of Retinoic Acid Sensitivity in Pancreatic Cancer.
S. Gupta, D. Pramanik, R. Mukherjee, N. R. Campbell, S. Elumalai, R. F. de Wilde, S.-M. Hong, M. G. Goggins, A. De Jesus-Acosta, D. Laheru, et al. (2012)
Clin. Cancer Res. 18, 280-289
   Abstract »    Full Text »    PDF »
A Polymeric Nanoparticle Encapsulated Small-Molecule Inhibitor of Hedgehog Signaling (NanoHHI) Bypasses Secondary Mutational Resistance to Smoothened Antagonists.
V. Chenna, C. Hu, D. Pramanik, B. T. Aftab, C. Karikari, N. R. Campbell, S.-M. Hong, M. Zhao, M. A. Rudek, S. R. Khan, et al. (2012)
Mol. Cancer Ther. 11, 165-173
   Abstract »    Full Text »    PDF »
Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways.
J. Wu, Y. Jiao, M. Dal Molin, A. Maitra, R. F. de Wilde, L. D. Wood, J. R. Eshleman, M. G. Goggins, C. L. Wolfgang, M. I. Canto, et al. (2011)
PNAS 108, 21188-21193
   Abstract »    Full Text »    PDF »
Locally Advanced Pancreatic Cancer: Where Should We Go From Here?.
P. A. Philip (2011)
J. Clin. Oncol. 29, 4066-4068
   Full Text »    PDF »
Pancreatic Ductal and Acinar Cell Neoplasms in Carney Complex: A Possible New Association.
S. Gaujoux, F. Tissier, B. Ragazzon, V. Rebours, E. Saloustros, K. Perlemoine, C. Vincent-Dejean, G. Meurette, E. Cassagnau, B. Dousset, et al. (2011)
J. Clin. Endocrinol. Metab. 96, E1888-E1895
   Abstract »    Full Text »    PDF »
Toll-like Receptor 9 Agonist IMO Cooperates with Cetuximab in K-Ras Mutant Colorectal and Pancreatic Cancers.
R. Rosa, D. Melisi, V. Damiano, R. Bianco, S. Garofalo, T. Gelardi, S. Agrawal, F. Di Nicolantonio, A. Scarpa, A. Bardelli, et al. (2011)
Clin. Cancer Res. 17, 6531-6541
   Abstract »    Full Text »    PDF »
Nuclear receptor liver receptor homologue 1 (LRH-1) regulates pancreatic cancer cell growth and proliferation.
C. Benod, M. V. Vinogradova, N. Jouravel, G. E. Kim, R. J. Fletterick, and E. P. Sablin (2011)
PNAS 108, 16927-16931
   Abstract »    Full Text »    PDF »
Exome sequencing identifies a spectrum of mutation frequencies in advanced and lethal prostate cancers.
A. Kumar, T. A. White, A. P. MacKenzie, N. Clegg, C. Lee, R. F. Dumpit, I. Coleman, S. B. Ng, S. J. Salipante, M. J. Rieder, et al. (2011)
PNAS 108, 17087-17092
   Abstract »    Full Text »    PDF »
A global insight into a cancer transcriptional space using pancreatic data: importance, findings and flaws.
E. Gadaleta, R. J. Cutts, G. P. Kelly, T. Crnogorac-Jurcevic, H. M. Kocher, N. R. Lemoine, and C. Chelala (2011)
Nucleic Acids Res. 39, 7900-7907
   Abstract »    Full Text »    PDF »
cMyc Is a Principal Upstream Driver of {beta}-Cell Proliferation in Rat Insulinoma Cell Lines and Is an Effective Mediator of Human {beta}-Cell Replication.
E. Karslioglu, J. W. Kleinberger, F. G. Salim, A. E. Cox, K. K. Takane, D. K. Scott, and A. F. Stewart (2011)
Mol. Endocrinol. 25, 1760-1772
   Abstract »    Full Text »    PDF »
Integrated Proteomic Profiling of Cell Line Conditioned Media and Pancreatic Juice for the Identification of Pancreatic Cancer Biomarkers.
S. Makawita, C. Smith, I. Batruch, Y. Zheng, F. Ruckert, R. Grutzmann, C. Pilarsky, S. Gallinger, and E. P. Diamandis (2011)
Mol. Cell. Proteomics 10, M111.008599
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882