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Published Online March 11, 2004
Science DOI: 10.1126/science.1096502

Brevia

Submitted on February 6, 2004
Accepted on February 27, 2004

High Frequency of Mutations of the PIK3CA Gene in Human Cancers

Yardena Samuels 1, Zhenghe Wang 1, Alberto Bardelli 1, Natalie Silliman 1, Janine Ptak 1, Steve Szabo 1, Hai Yan 2, Adi Gazdar 3, Steven M. Powell 4, Gregory J. Riggins 1, James K.V. Willson 5, Sanford Markowitz 5, Kenneth W. Kinzler 1, Bert Vogelstein 1, Victor E. Velculescu 1*

1 The Sidney Kimmel Comprehensive Cancer Center and The Howard Hughes Medical Institute, The Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA.
2 Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
3 Hamon Center for Therapeutic Oncology Research and Dept. of Pathology, UT Southwestern Medical Center, Dallas TX 75390, USA.
4 Division of Gastroenterology/Hepatology, UVA Health System, Charlottesville, VA 22908, USA.
5 Howard Hughes Medical Institute and Ireland Cancer Center, University Hospitals of Cleveland and Case Western University, Cleveland, OH 44106, USA.

* To whom correspondence should be addressed. E-mail: velculescu{at}jhmi.edu.

A gene coding for a well-known lipid kinase is frequently mutated in human tumors, offering a new target for cancer diagnosis and therapy.


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L. M. Ballou, E. S. Selinger, J. Y. Choi, D. G. Drueckhammer, and R. Z. Lin (2007)
J. Biol. Chem. 282, 24463-24470
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Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern.
C. Hafner, E. Lopez-Knowles, N. M. Luis, A. Toll, E. Baselga, A. Fernandez-Casado, S. Hernandez, A. Ribe, T. Mentzel, R. Stoehr, et al. (2007)
PNAS 104, 13450-13454
   Abstract »    Full Text »    PDF »
The Role of Phosphoinositide 3-Kinase Pathway Inhibitors in the Treatment of Lung Cancer.
J. A. Engelman (2007)
Clin. Cancer Res. 13, 4637s-4640s
   Abstract »    Full Text »    PDF »
Mechanism of Two Classes of Cancer Mutations in the Phosphoinositide 3-Kinase Catalytic Subunit.
N. Miled, Y. Yan, W.-C. Hon, O. Perisic, M. Zvelebil, Y. Inbar, D. Schneidman-Duhovny, H. J. Wolfson, J. M. Backer, and R. L. Williams (2007)
Science 317, 239-242
   Abstract »    Full Text »    PDF »
The p110{alpha} Isoform of Phosphatidylinositol 3-Kinase Is Essential for Polyomavirus Middle T Antigen-Mediated Transformation.
T. Utermark, B. S. Schaffhausen, T. M. Roberts, and J. J. Zhao (2007)
J. Virol. 81, 7069-7076
   Abstract »    Full Text »    PDF »
Mucinous Differentiation Correlates with Absence of EGFR Mutation and Presence of KRAS Mutation in Lung Adenocarcinomas with Bronchioloalveolar Features.
K. E. Finberg, L. V. Sequist, V. A. Joshi, A. Muzikansky, J. M. Miller, M. Han, J. Beheshti, L. R. Chirieac, E. J. Mark, and A. J. Iafrate (2007)
J. Mol. Diagn. 9, 320-326
   Abstract »    Full Text »    PDF »
PTEN, more than the AKT pathway.
C. Blanco-Aparicio, O. Renner, J. F.M. Leal, and A. Carnero (2007)
Carcinogenesis 28, 1379-1386
   Abstract »    Full Text »    PDF »
Cancer genomics: integrating form and function.
S. Y. Kim and W. C. Hahn (2007)
Carcinogenesis 28, 1387-1392
   Abstract »    Full Text »    PDF »
Pharmacologic Characterization of a Potent Inhibitor of Class I Phosphatidylinositide 3-Kinases.
F. I. Raynaud, S. Eccles, P. A. Clarke, A. Hayes, B. Nutley, S. Alix, A. Henley, F. Di-Stefano, Z. Ahmad, S. Guillard, et al. (2007)
Cancer Res. 67, 5840-5850
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Mutant PIK3CA-Bearing Colon Cancer Cells Display Increased Metastasis in an Orthotopic Model.
X.-N. Guo, A. Rajput, R. Rose, J. Hauser, A. Beko, K. Kuropatwinski, C. LeVea, R. M. Hoffman, M. G. Brattain, and J. Wang (2007)
Cancer Res. 67, 5851-5858
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PIK3CA Mutations and PTEN Loss Correlate with Similar Prognostic Factors and Are Not Mutually Exclusive in Breast Cancer.
G. Perez-Tenorio, L. Alkhori, B. Olsson, M. A. Waltersson, B. Nordenskjold, L. E. Rutqvist, L. Skoog, and O. Stal (2007)
Clin. Cancer Res. 13, 3577-3584
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Genetic and epigenetic profiling in early colorectal tumors and prediction of invasive potential in pT1 (early invasive) colorectal cancers.
K. Nosho, H. Yamamoto, T. Takahashi, M. Mikami, H. Taniguchi, N. Miyamoto, Y. Adachi, Y. Arimura, F. Itoh, K. Imai, et al. (2007)
Carcinogenesis 28, 1364-1370
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A New Crucial Protein Interaction Element That Targets the Adenovirus E4-ORF1 Oncoprotein to Membrane Vesicles.
S.-H. Chung, K. K. Frese, R. S. Weiss, B. V. V. Prasad, and R. T. Javier (2007)
J. Virol. 81, 4787-4797
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Rare cancer-specific mutations in PIK3CA show gain of function.
M. Gymnopoulos, M.-A. Elsliger, and P. K. Vogt (2007)
PNAS 104, 5569-5574
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Colon carcinoma cells harboring PIK3CA mutations display resistance to growth factor deprivation induced apoptosis.
J. Wang, K. Kuropatwinski, J. Hauser, M. R. Rossi, Y. Zhou, A. Conway, J. L.C. Kan, N. W. Gibson, J. K.V. Willson, J. K. Cowell, et al. (2007)
Mol. Cancer Ther. 6, 1143-1150
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Clinical and Molecular Characteristics of Malignant Transformation of Low-Grade Glioma in Children.
A. Broniscer, S. J. Baker, A. N. West, M. M. Fraser, E. Proko, M. Kocak, J. Dalton, G. P. Zambetti, D. W. Ellison, L. E. Kun, et al. (2007)
J. Clin. Oncol. 25, 682-689
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Lung premalignancy induced by mutant B-Raf, what is thy fate? To senesce or not to senesce, that is the question.
K. M. Haigis, I. I. Wistuba, and J. M. Kurie (2007)
Genes & Dev. 21, 361-366
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Genetic Alterations and Their Relationship in the Phosphatidylinositol 3-Kinase/Akt Pathway in Thyroid Cancer.
P. Hou, D. Liu, Y. Shan, S. Hu, K. Studeman, S. Condouris, Y. Wang, A. Trink, A. K. El-Naggar, G. Tallini, et al. (2007)
Clin. Cancer Res. 13, 1161-1170
   Abstract »    Full Text »    PDF »
Mitogen-activated Protein Kinase Kinase-4 Promotes Cell Survival by Decreasing PTEN Expression through an NF{kappa}B-dependent Pathway.
D. Xia, H. Srinivas, Y.-h. Ahn, G. Sethi, X. Sheng, W. K. A. Yung, Q. Xia, P. J. Chiao, H. Kim, P. H. Brown, et al. (2007)
J. Biol. Chem. 282, 3507-3519
   Abstract »    Full Text »    PDF »
Phosphatidylinositol-3-OH Kinase or RAS Pathway Mutations in Human Breast Cancer Cell Lines.
A. Hollestelle, F. Elstrodt, J. H.A. Nagel, W. W. Kallemeijn, and M. Schutte (2007)
Mol. Cancer Res. 5, 195-201
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Combination of sublethal concentrations of epidermal growth factor receptor inhibitor and microtubule stabilizer induces apoptosis of glioblastoma cells.
M. Failly, S. Korur, V. Egler, J.-L. Boulay, M. M. Lino, R. Imber, and A. Merlo (2007)
Mol. Cancer Ther. 6, 773-781
   Abstract »    Full Text »    PDF »
Distinguishing Cancer-Associated Missense Mutations from Common Polymorphisms.
J. S. Kaminker, Y. Zhang, A. Waugh, P. M. Haverty, B. Peters, D. Sebisanovic, J. Stinson, W. F. Forrest, J. F. Bazan, S. Seshagiri, et al. (2007)
Cancer Res. 67, 465-473
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Activation of Akt Predicts Poor Outcome in Neuroblastoma.
D. Opel, C. Poremba, T. Simon, K.-M. Debatin, and S. Fulda (2007)
Cancer Res. 67, 735-745
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Activation of p53-Dependent Growth Suppression in Human Cells by Mutations in PTEN or PIK3CA.
J.-S. Kim, C. Lee, C. L. Bonifant, H. Ressom, and T. Waldman (2007)
Mol. Cell. Biol. 27, 662-677
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Clinicopathologic Analysis of Breast Cancers with PIK3CA Mutations in Japanese Women.
N. Maruyama, Y. Miyoshi, T. Taguchi, Y. Tamaki, M. Monden, and S. Noguchi (2007)
Clin. Cancer Res. 13, 408-414
   Abstract »    Full Text »    PDF »
PI3 Kinases in Cancer: From Oncogene Artifact to Leading Cancer Target.
J. J. Zhao and T. M. Roberts (2006)
Sci. STKE 2006, pe52
   Abstract »    Full Text »    PDF »
Phosphatidylinositol 3-Kinase-dependent Modulation of Carnitine Palmitoyltransferase 1A Expression Regulates Lipid Metabolism during Hematopoietic Cell Growth.
R. J. DeBerardinis, J. J. Lum, and C. B. Thompson (2006)
J. Biol. Chem. 281, 37372-37380
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Improved Marker Combination for Detection of De Novo Genetic Variation and Aberrant DNA in Colorectal Neoplasia.
L. Kann, J. Han, D. Ahlquist, T. Levin, D. Rex, D. Whitney, S. Markowitz, and A. Shuber (2006)
Clin. Chem. 52, 2299-2302
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PIK3CA and PTEN Mutations in Uterine Endometrioid Carcinoma and Complex Atypical Hyperplasia..
M. P. Hayes, H. Wang, R. Espinal-Witter, W. Douglas, G. J. Solomon, S. J. Baker, and L. H. Ellenson (2006)
Clin. Cancer Res. 12, 5932-5935
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PIK3CA Gene Mutations in Pediatric and Adult Glioblastoma Multiforme.
G. L. Gallia, V. Rand, I-M. Siu, C. G. Eberhart, C. D. James, S. K.N. Marie, S. M. Oba-Shinjo, C. G. Carlotti, O. L. Caballero, A. J.G. Simpson, et al. (2006)
Mol. Cancer Res. 4, 709-714
   Abstract »    Full Text »    PDF »


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