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 333 (6046): 1154-1157

Copyright © 2011 by the American Association for the Advancement of Science

Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1

Nishant Agrawal,1,2,*,{dagger} Mitchell J. Frederick,3,* Curtis R. Pickering,3,* Chetan Bettegowda,2,4,* Kyle Chang,5 Ryan J. Li,1 Carole Fakhry,1 Tong-Xin Xie,3 Jiexin Zhang,6 Jing Wang,6 Nianxiang Zhang,6 Adel K. El-Naggar,7 Samar A. Jasser,3 John N. Weinstein,6 Lisa Treviño,5 Jennifer A. Drummond,5 Donna M. Muzny,5 Yuanqing Wu,5 Laura D. Wood,8 Ralph H. Hruban,8 William H. Westra,8 Wayne M. Koch,1 Joseph A. Califano,1,9 Richard A. Gibbs,5,9 David Sidransky,1 Bert Vogelstein,2 Victor E. Velculescu,2,{dagger} Nickolas Papadopoulos,2 David A. Wheeler,5 Kenneth W. Kinzler,2,{dagger} Jeffrey N. Myers3,{dagger}

Abstract: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To explore the genetic origins of this cancer, we used whole-exome sequencing and gene copy number analyses to study 32 primary tumors. Tumors from patients with a history of tobacco use had more mutations than did tumors from patients who did not use tobacco, and tumors that were negative for human papillomavirus (HPV) had more mutations than did HPV-positive tumors. Six of the genes that were mutated in multiple tumors were assessed in up to 88 additional HNSCCs. In addition to previously described mutations in TP53, CDKN2A, PIK3CA, and HRAS, we identified mutations in FBXW7 and NOTCH1. Nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type.

1 Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA.
2 Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.
3 Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
4 Department of Neurosurgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA.
5 Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
6 Department of Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
7 Department of Pathology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
8 Department of Pathology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA.
9 Milton J. Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, MD 21204, USA.
10 Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: nagrawal{at}jhmi.edu (N.A.); velculescu{at}jhmi.edu (V.E.V.); kinzlke{at}jhmi.edu (K.W.K.); jmyers{at}mdanderson.org (J.N.M.)


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Harnessing Massively Parallel Sequencing in Personalized Head and Neck Oncology.
M. Jessri and C. S. Farah (2014)
Journal of Dental Research 93, 437-444
   Abstract »    Full Text »    PDF »
Notch signaling: switching an oncogene to a tumor suppressor.
C. Lobry, P. Oh, M. R. Mansour, A. T. Look, and I. Aifantis (2014)
Blood 123, 2451-2459
   Abstract »    Full Text »    PDF »
Bioluminescent Imaging of HPV-Positive Oral Tumor Growth and Its Response to Image-Guided Radiotherapy.
R. Zhong, M. Pytynia, C. Pelizzari, and M. Spiotto (2014)
Cancer Res. 74, 2073-2081
   Abstract »    Full Text »    PDF »
Genomic Analysis of Head and Neck Squamous Cell Carcinoma Cell Lines and Human Tumors: A Rational Approach to Preclinical Model Selection.
H. Li, J. S. Wawrose, W. E. Gooding, L. A. Garraway, V. W. Y. Lui, N. D. Peyser, and J. R. Grandis (2014)
Mol. Cancer Res. 12, 571-582
   Abstract »    Full Text »    PDF »
Phase I Study of Oral Rigosertib (ON 01910.Na), a Dual Inhibitor of the PI3K and Plk1 Pathways, in Adult Patients with Advanced Solid Malignancies.
D. W. Bowles, J. R. Diamond, E. T. Lam, C. D. Weekes, D. P. Astling, R. T. Anderson, S. Leong, L. Gore, M. Varella-Garcia, B. W. Vogler, et al. (2014)
Clin. Cancer Res. 20, 1656-1665
   Abstract »    Full Text »    PDF »
NCG 4.0: the network of cancer genes in the era of massive mutational screenings of cancer genomes.
O. An, V. Pendino, M. D'Antonio, E. Ratti, M. Gentilini, and F. D. Ciccarelli (2014)
Database 2014, bau015
   Abstract »    Full Text »    PDF »
Identifying driver mutations from sequencing data of heterogeneous tumors in the era of personalized genome sequencing.
J. Zhang, J. Liu, J. Sun, C. Chen, G. Foltz, and B. Lin (2014)
Brief Bioinform 15, 244-255
   Abstract »    Full Text »    PDF »
Impairing squamous differentiation by Klf4 deletion is sufficient to initiate tongue carcinoma development upon K-Ras activation in mice.
M. Abrigo, R. Alvarez, M. L. Paparella, D. E. Calb, E. Bal de Kier Joffe, J. S. Gutkind, and A. R. Raimondi (2014)
Carcinogenesis 35, 662-669
   Abstract »    Full Text »    PDF »
Chemoprevention of Squamous Cell Carcinoma of the Head and Neck: No Time to Lose Momentum.
L. J. Wirth (2014)
Cancer Prevention Research 7, 279-282
   Abstract »    Full Text »    PDF »
Activation of the NOTCH Pathway in Head and Neck Cancer.
W. Sun, D. A. Gaykalova, M. F. Ochs, E. Mambo, D. Arnaoutakis, Y. Liu, M. Loyo, N. Agrawal, J. Howard, R. Li, et al. (2014)
Cancer Res. 74, 1091-1104
   Abstract »    Full Text »    PDF »
Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability.
K. Akagi, J. Li, T. R. Broutian, H. Padilla-Nash, W. Xiao, B. Jiang, J. W. Rocco, T. N. Teknos, B. Kumar, D. Wangsa, et al. (2014)
Genome Res. 24, 185-199
   Abstract »    Full Text »    PDF »
Common and Complex Notch1 Mutations in Chinese Oral Squamous Cell Carcinoma.
X. Song, R. Xia, J. Li, Z. Long, H. Ren, W. Chen, and L. Mao (2014)
Clin. Cancer Res. 20, 701-710
   Abstract »    Full Text »    PDF »
Direct in Vivo RNAi Screen Unveils Myosin IIa as a Tumor Suppressor of Squamous Cell Carcinomas.
D. Schramek, A. Sendoel, J. P. Segal, S. Beronja, E. Heller, D. Oristian, B. Reva, and E. Fuchs (2014)
Science 343, 309-313
   Abstract »    Full Text »    PDF »
Aberrant epidermal differentiation and disrupted {Delta}Np63/Notch regulatory axis in Ets1 transgenic mice.
S. S. Chin, R.-A. Romano, P. Nagarajan, S. Sinha, and L. A. Garrett-Sinha (2013)
Biology Open 2, 1336-1345
   Abstract »    Full Text »    PDF »
Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974.
J. Liu, S. Pan, M. H. Hsieh, N. Ng, F. Sun, T. Wang, S. Kasibhatla, A. G. Schuller, A. G. Li, D. Cheng, et al. (2013)
PNAS 110, 20224-20229
   Abstract »    Full Text »    PDF »
Cutaneous Notch Signaling in Health and Disease.
C. Nowell and F. Radtke (2013)
Cold Spring Harb Perspect Med 3, a017772
   Abstract »    Full Text »    PDF »
The Dual Pathway Inhibitor Rigosertib Is Effective in Direct Patient Tumor Xenografts of Head and Neck Squamous Cell Carcinomas.
R. T. Anderson, S. B. Keysar, D. W. Bowles, M. J. Glogowska, D. P. Astling, J. J. Morton, P. Le, A. Umpierrez, J. Eagles-Soukup, G. N. Gan, et al. (2013)
Mol. Cancer Ther. 12, 1994-2005
   Abstract »    Full Text »    PDF »
CT Imaging Correlates of Genomic Expression for Oral Cavity Squamous Cell Carcinoma.
C. R. Pickering, K. Shah, S. Ahmed, A. Rao, M. J. Frederick, J. Zhang, A. K. Unruh, J. Wang, L. E. Ginsberg, A. J. Kumar, et al. (2013)
AJNR Am. J. Neuroradiol. 34, 1818-1822
   Abstract »    Full Text »    PDF »
Epigenetic Modulation of Signal Transduction Pathways in HPV-Associated HNSCC.
M. J. Worsham, K. M. Chen, T. Ghanem, J. K. Stephen, and G. Divine (2013)
Otolaryngology -- Head and Neck Surgery 149, 409-416
   Abstract »    Full Text »    PDF »
Chk1/2 Inhibition Overcomes the Cisplatin Resistance of Head and Neck Cancer Cells Secondary to the Loss of Functional p53.
M. A. Gadhikar, M. R. Sciuto, M. V. O. Alves, C. R. Pickering, A. A. Osman, D. M. Neskey, M. Zhao, A. L. Fitzgerald, J. N. Myers, and M. J. Frederick (2013)
Mol. Cancer Ther. 12, 1860-1873
   Abstract »    Full Text »    PDF »
Inhibitor-Sensitive FGFR2 and FGFR3 Mutations in Lung Squamous Cell Carcinoma.
R. G. Liao, J. Jung, J. Tchaicha, M. D. Wilkerson, A. Sivachenko, E. M. Beauchamp, Q. Liu, T. J. Pugh, C. S. Pedamallu, D. N. Hayes, et al. (2013)
Cancer Res. 73, 5195-5205
   Abstract »    Full Text »    PDF »
A miR-34a-SIRT6 axis in the squamous cell differentiation network.
K. Lefort, Y. Brooks, P. Ostano, M. Cario-Andre, V. Calpini, J. Guinea-Viniegra, A. Albinger-Hegyi, W. Hoetzenecker, I. Kolfschoten, E. F. Wagner, et al. (2013)
EMBO J. 32, 2248-2263
   Abstract »    Full Text »    PDF »
Mutational Signature of Aristolochic Acid Exposure as Revealed by Whole-Exome Sequencing.
M. L. Hoang, C.-H. Chen, V. S. Sidorenko, J. He, K. G. Dickman, B. H. Yun, M. Moriya, N. Niknafs, C. Douville, R. Karchin, et al. (2013)
Science Translational Medicine 5, 197ra102
   Abstract »    Full Text »    PDF »
Enhanced Radiation Sensitivity in HPV-Positive Head and Neck Cancer.
R. J. Kimple, M. A. Smith, G. C. Blitzer, A. D. Torres, J. A. Martin, R. Z. Yang, C. R. Peet, L. D. Lorenz, K. P. Nickel, A. J. Klingelhutz, et al. (2013)
Cancer Res. 73, 4791-4800
   Abstract »    Full Text »    PDF »
A Poor Prognosis Subtype of HNSCC Is Consistently Observed across Methylome, Transcriptome, and miRNome Analysis.
A. C. Jung, S. Job, S. Ledrappier, C. Macabre, J. Abecassis, A. de Reynies, and B. Wasylyk (2013)
Clin. Cancer Res. 19, 4174-4184
   Abstract »    Full Text »    PDF »
Exploiting the Head and Neck Cancer Oncogenome: Widespread PI3K-mTOR Pathway Alterations and Novel Molecular Targets.
R. Iglesias-Bartolome, D. Martin, and J. S. Gutkind (2013)
Cancer Discovery 3, 722-725
   Abstract »    Full Text »    PDF »
Frequent Mutation of the PI3K Pathway in Head and Neck Cancer Defines Predictive Biomarkers.
V. W. Y. Lui, M. L. Hedberg, H. Li, B. S. Vangara, K. Pendleton, Y. Zeng, Y. Lu, Q. Zhang, Y. Du, B. R. Gilbert, et al. (2013)
Cancer Discovery 3, 761-769
   Abstract »    Full Text »    PDF »
Integrative Genomic Characterization of Oral Squamous Cell Carcinoma Identifies Frequent Somatic Drivers.
C. R. Pickering, J. Zhang, S. Y. Yoo, L. Bengtsson, S. Moorthy, D. M. Neskey, M. Zhao, M. V. Ortega Alves, K. Chang, J. Drummond, et al. (2013)
Cancer Discovery 3, 770-781
   Abstract »    Full Text »    PDF »
Expanding the Foundation for Personalized Medicine: Implications and Challenges for Dentistry.
I. Garcia, R. Kuska, and M. J. Somerman (2013)
Journal of Dental Research 92, S3-S10
   Abstract »    Full Text »    PDF »
Progression of genotype-specific oral cancer leads to senescence of cancer-associated fibroblasts and is mediated by oxidative stress and TGF-{beta}.
Y. Hassona, N. Cirillo, K. P. Lim, A. Herman, M. Mellone, G. J. Thomas, G. N. Pitiyage, E. K. Parkinson, and S. S. Prime (2013)
Carcinogenesis 34, 1286-1295
   Abstract »    Full Text »    PDF »
Notch3 Functions as a Tumor Suppressor by Controlling Cellular Senescence.
H. Cui, Y. Kong, M. Xu, and H. Zhang (2013)
Cancer Res. 73, 3451-3459
   Abstract »    Full Text »    PDF »
Genomics of Squamous Cell Lung Cancer.
M. Rooney, S. Devarakonda, and R. Govindan (2013)
Oncologist 18, 707-716
   Abstract »    Full Text »    PDF »
Understanding the Determinants of Notch Interactions with Its Ligands.
J. F. de Celis (2013)
Science Signaling 6, pe19
   Abstract »    Full Text »    PDF »
Genomics-Driven Oncology: Framework for an Emerging Paradigm.
L. A. Garraway (2013)
J. Clin. Oncol. 31, 1806-1814
   Abstract »    Full Text »    PDF »
Clinical Correlates of Promoter Hypermethylation of Four Target Genes in Head and Neck Cancer: A Cooperative Group Correlative Study.
J.-L. Roh, X. V. Wang, J. Manola, D. Sidransky, A. A. Forastiere, and W. M. Koch (2013)
Clin. Cancer Res. 19, 2528-2540
   Abstract »    Full Text »    PDF »
Head and Neck Squamous Cell Carcinoma Sequenced.
Kenneth Y. Tsai, MD, PhD and Kenneth Y. Tsai, MD, PhD (2013)
Journal Watch 2011, JD201109230000003
   Full Text »
Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia.
B. Diaz, A. Yuen, S. Iizuka, S. Higashiyama, and S. A. Courtneidge (2013)
J. Cell Biol. 201, 279-292
   Abstract »    Full Text »    PDF »
A Receptor Tyrosine Kinase Network Composed of Fibroblast Growth Factor Receptors, Epidermal Growth Factor Receptor, v-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog 2, and Hepatocyte Growth Factor Receptor Drives Growth and Survival of Head and Neck Squamous Carcinoma Cell Lines.
K. R. Singleton, J. Kim, T. K. Hinz, L. A. Marek, M. Casas-Selves, C. Hatheway, A. C. Tan, J. DeGregori, and L. E. Heasley (2013)
Mol. Pharmacol. 83, 882-893
   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 »
Evidence for a Role of the PD-1:PD-L1 Pathway in Immune Resistance of HPV-Associated Head and Neck Squamous Cell Carcinoma.
S. Lyford-Pike, S. Peng, G. D. Young, J. M. Taube, W. H. Westra, B. Akpeng, T. C. Bruno, J. D. Richmon, H. Wang, J. A. Bishop, et al. (2013)
Cancer Res. 73, 1733-1741
   Abstract »    Full Text »    PDF »
Bcl-2 Inhibition or FBXW7 Mutation Sensitizes Solid Tumor Cells to HDAC Inhibition In Vitro but Could Prove Difficult to Validate in Patients.
C. R. Pickering and J. N. Myers (2013)
Cancer Discovery 3, 258-259
   Abstract »    Full Text »    PDF »
Description of the Developmental Patterns of Epithelial Cells and Cancers Originating from Them Will Provide Many Sites for Therapy.
K. M. ANDERSON, P. GUINAN, and M. RUBENSTEIN (2013)
In Vivo 27, 159-163
   Abstract »    Full Text »    PDF »
Competing Roads to Larynx Preservation.
E. E. Vokes (2013)
J. Clin. Oncol. 31, 833-835
   Full Text »    PDF »
Mcl-1 and FBW7 Control a Dominant Survival Pathway Underlying HDAC and Bcl-2 Inhibitor Synergy in Squamous Cell Carcinoma.
L. He, K. Torres-Lockhart, N. Forster, S. Ramakrishnan, P. Greninger, M. J. Garnett, U. McDermott, S. M. Rothenberg, C. H. Benes, and L. W. Ellisen (2013)
Cancer Discovery 3, 324-337
   Abstract »    Full Text »    PDF »
Notch pathway activation targets AML-initiating cell homeostasis and differentiation.
C. Lobry, P. Ntziachristos, D. Ndiaye-Lobry, P. Oh, L. Cimmino, N. Zhu, E. Araldi, W. Hu, J. Freund, O. Abdel-Wahab, et al. (2013)
J. Exp. Med. 210, 301-319
   Abstract »    Full Text »    PDF »
Deep Sequencing in Cancer Research.
K. Yoshida, M. Sanada, and S. Ogawa (2013)
Jpn. J. Clin. Oncol. 43, 110-115
   Abstract »    Full Text »    PDF »
Dysregulation of the Repressive H3K27 Trimethylation Mark in Head and Neck Squamous Cell Carcinoma Contributes to Dysregulated Squamous Differentiation.
O. M. Gannon, L. Merida de Long, L. Endo-Munoz, M. Hazar-Rethinam, and N. A. Saunders (2013)
Clin. Cancer Res. 19, 428-441
   Abstract »    Full Text »    PDF »
A Mutation in EGF Repeat-8 of Notch Discriminates Between Serrate/Jagged and Delta Family Ligands.
S. Yamamoto, W.-L. Charng, N. A. Rana, S. Kakuda, M. Jaiswal, V. Bayat, B. Xiong, K. Zhang, H. Sandoval, G. David, et al. (2012)
Science 338, 1229-1232
   Abstract »    Full Text »    PDF »
Functional impact bias reveals cancer drivers.
A. Gonzalez-Perez and N. Lopez-Bigas (2012)
Nucleic Acids Res. 40, e169
   Abstract »    Full Text »    PDF »
Enterococcus faecalis Enhances Cell Proliferation through Hydrogen Peroxide-Mediated Epidermal Growth Factor Receptor Activation.
K. Boonanantanasarn, A. L. Gill, Y. Yap, V. Jayaprakash, M. A. Sullivan, and S. R. Gill (2012)
Infect. Immun. 80, 3545-3558
   Abstract »    Full Text »    PDF »
Comparative Genomic Analysis of Esophageal Adenocarcinoma and Squamous Cell Carcinoma.
N. Agrawal, Y. Jiao, C. Bettegowda, S. M. Hutfless, Y. Wang, S. David, Y. Cheng, W. S. Twaddell, N. L. Latt, E. J. Shin, et al. (2012)
Cancer Discovery 2, 899-905
   Abstract »    Full Text »    PDF »
Notch Signaling.
R. Kopan (2012)
Cold Spring Harb Perspect Biol 4, a011213
   Full Text »    PDF »
Chemopreventive and Chemotherapeutic Actions of mTOR Inhibitor in Genetically Defined Head and Neck Squamous Cell Carcinoma Mouse Model.
Z.-J. Sun, L. Zhang, B. Hall, Y. Bian, J. S. Gutkind, and A. B. Kulkarni (2012)
Clin. Cancer Res. 18, 5304-5313
   Abstract »    Full Text »    PDF »
Molecular Pathways: Context-Dependent Approaches to Notch Targeting as Cancer Therapy.
A. M. Egloff and J. R. Grandis (2012)
Clin. Cancer Res. 18, 5188-5195
   Abstract »    Full Text »    PDF »
Gene expression signatures and molecular markers associated with clinical outcome in locally advanced head and neck carcinoma.
M. Pavon, M. Parreno, M. Tellez-Gabriel, F. Sancho, M. Lopez, M. Cespedes, I. Casanova, A. Lopez-Pousa, M. Mangues, M. Quer, et al. (2012)
Carcinogenesis 33, 1707-1716
   Abstract »    Full Text »    PDF »
Anti-tumor effects of the Notch pathway in gastrointestinal stromal tumors.
A. G. Dumont, Y. Yang, D. Reynoso, D. Katz, J. C. Trent, and D. P. Hughes (2012)
Carcinogenesis 33, 1674-1683
   Abstract »    Full Text »    PDF »
Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma.
M. J. Kiel, T. Velusamy, B. L. Betz, L. Zhao, H. G. Weigelin, M. Y. Chiang, D. R. Huebner-Chan, N. G. Bailey, D. T. Yang, G. Bhagat, et al. (2012)
J. Exp. Med. 209, 1553-1565
   Abstract »    Full Text »    PDF »
A Multicenter Phase I Trial of PX-866, an Oral Irreversible Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Advanced Solid Tumors.
D. S. Hong, D. W. Bowles, G. S. Falchook, W. A. Messersmith, G. C. George, C. L. O'Bryant, A. C. H. Vo, K. Klucher, R. S. Herbst, S. G. Eckhardt, et al. (2012)
Clin. Cancer Res. 18, 4173-4182
   Abstract »    Full Text »    PDF »
Targeting the Notch Pathway: Twists and Turns on the Road to Rational Therapeutics.
J. C. Aster and S. C. Blacklow (2012)
J. Clin. Oncol. 30, 2418-2420
   Full Text »    PDF »
TMEM16A Induces MAPK and Contributes Directly to Tumorigenesis and Cancer Progression.
U. Duvvuri, D. J. Shiwarski, D. Xiao, C. Bertrand, X. Huang, R. S. Edinger, J. R. Rock, B. D. Harfe, B. J. Henson, K. Kunzelmann, et al. (2012)
Cancer Res. 72, 3270-3281
   Abstract »    Full Text »    PDF »
Cutaneous {beta}-human papillomavirus E6 proteins bind Mastermind-like coactivators and repress Notch signaling.
M. J. A. Tan, E. A. White, M. E. Sowa, J. W. Harper, J. C. Aster, and P. M. Howley (2012)
PNAS 109, E1473-E1480
   Abstract »    Full Text »    PDF »
Tumor Epidermal Growth Factor Receptor and EGFR PY1068 Are Independent Prognostic Indicators for Head and Neck Squamous Cell Carcinoma.
S. Wheeler, D. R. Siwak, R. Chai, C. LaValle, R. R. Seethala, L. Wang, K. Cieply, C. Sherer, C. Joy, G. B. Mills, et al. (2012)
Clin. Cancer Res. 18, 2278-2289
   Abstract »    Full Text »    PDF »
A Phase II Study of Lapatinib in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck.
J. A. de Souza, D. W. Davis, Y. Zhang, A. Khattri, T. Y. Seiwert, S. Aktolga, S. J. Wong, M. F. Kozloff, S. Nattam, M. W. Lingen, et al. (2012)
Clin. Cancer Res. 18, 2336-2343
   Abstract »    Full Text »    PDF »
Metformin Prevents the Development of Oral Squamous Cell Carcinomas from Carcinogen-Induced Premalignant Lesions.
L. Vitale-Cross, A. A. Molinolo, D. Martin, R. H. Younis, T. Maruyama, V. Patel, W. Chen, A. Schneider, and J. S. Gutkind (2012)
Cancer Prevention Research 5, 562-573
   Abstract »    Full Text »    PDF »
Re: Delta-Like Ligand 4-Notch Blockade and Tumor Radiation Response.
S. Masuda (2012)
J Natl Cancer Inst 104, 421
   Full Text »    PDF »
Response: Re: Delta-Like Ligand 4-Notch Blockade and Tumor Radiation Response.
S. K. Liu, R. J. Muschel, and A. L. Harris (2012)
J Natl Cancer Inst 104, 421-422
   Full Text »    PDF »
Pocket Proteins Suppress Head and Neck Cancer.
M.-K. Shin, H. C. Pitot, and P. F. Lambert (2012)
Cancer Res. 72, 1280-1289
   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 »
ERK1/2 Regulation of CD44 Modulates Oral Cancer Aggressiveness.
N. P. Judd, A. E. Winkler, O. Murillo-Sauca, J. J. Brotman, J. H. Law, J. S. Lewis Jr, G. P. Dunn, J. D. Bui, J. B. Sunwoo, and R. Uppaluri (2012)
Cancer Res. 72, 365-374
   Abstract »    Full Text »    PDF »
TP53 Disruptive Mutations Lead to Head and Neck Cancer Treatment Failure through Inhibition of Radiation-Induced Senescence.
H. D. Skinner, V. C. Sandulache, T. J. Ow, R. E. Meyn, J. S. Yordy, B. M. Beadle, A. L. Fitzgerald, U. Giri, K. K. Ang, and J. N. Myers (2012)
Clin. Cancer Res. 18, 290-300
   Abstract »    Full Text »    PDF »
Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma.
N. J. Wang, Z. Sanborn, K. L. Arnett, L. J. Bayston, W. Liao, C. M. Proby, I. M. Leigh, E. A. Collisson, P. B. Gordon, L. Jakkula, et al. (2011)
PNAS 108, 17761-17766
   Abstract »    Full Text »    PDF »
Oncogenic and tumor suppressor functions of Notch in cancer: it's NOTCH what you think.
C. Lobry, P. Oh, and I. Aifantis (2011)
J. Exp. Med. 208, 1931-1935
   Abstract »    Full Text »    PDF »
Head and Neck Squamous Cell Carcinoma Sequenced.
(2011)
Journal Watch Dermatology 2011, 3
   Full Text »
Understanding the Enemy.
V. E. Velculescu and L. A. Diaz Jr. (2011)
Science Translational Medicine 3, 98ps37
   Full Text »    PDF »
Another NOTCH for Cancer.
R. H. Brakenhoff (2011)
Science 333, 1102-1103
   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