Cancer Research Meeting Calendar Telomeres
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Oda, K.
Right arrow Articles by McCormick, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oda, K.
Right arrow Articles by McCormick, F.
[Cancer Research 65, 10669-10673, December 1, 2005]
© 2005 American Association for Cancer Research

Priority Reports

High Frequency of Coexistent Mutations of PIK3CA and PTEN Genes in Endometrial Carcinoma

Katsutoshi Oda1,2, David Stokoe1, Yuji Taketani2 and Frank McCormick1

1 Cancer Research Institute, University of California San Francisco, San Francisco, California and 2 Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo, Japan

Requests for reprints: Frank McCormick, University of California San Francisco, Cancer Research Institute, 2340 Sutter Street, N-331, UCSF Box 0128, San Francisco, CA 94115. Phone: 415-502-1710; Fax: 415-502-1712; E-mail: mccormick{at}cc.ucsf.edu.

The phosphatidylinositol 3'-kinase (PI3K) pathway is activated in many human cancers. In addition to inactivation of the PTEN tumor suppressor gene, mutations or amplifications of the catalytic subunit {alpha} of PI3K (PIK3CA) have been reported. However, the coexistence of mutations in these two genes seems exceedingly rare. As PTEN mutations occur at high frequency in endometrial carcinoma, we screened 66 primary endometrial carcinomas for mutations in the helical and catalytic domains of PIK3CA. We identified a total of 24 (36%) mutations in this gene and coexistence of PIK3CA/PTEN mutations at high frequency (26%). PIK3CA mutations were more common in tumors with PTEN mutations (17 of 37, 46%) compared with those without PTEN mutations (7 of 29, 24%). Array comparative genomic hybridization detected 3q24-qter amplification, which covers the PIK3CA gene (3q26.3), in one of nine tumors. Knocking down PTEN expression in the HEC-1B cell line, which possesses both K-Ras and PIK3CA mutations, further enhances phosphorylation of Akt (Ser473), indicating that double mutation of PIK3CA and PTEN has an additive effect on PI3K activation. Our data suggest that the PI3K pathway is extensively activated in endometrial carcinomas, and that combination of PIK3CA/PTEN alterations might play an important role in development of these tumors.




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
F. M. Platt, C. D. Hurst, C. F. Taylor, W. M. Gregory, P. Harnden, and M. A. Knowles
Spectrum of Phosphatidylinositol 3-Kinase Pathway Gene Alterations in Bladder Cancer
Clin. Cancer Res., October 1, 2009; 15(19): 6008 - 6017.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
D Llobet, J Pallares, A Yeramian, M Santacana, N Eritja, A Velasco, X Dolcet, and X Matias-Guiu
Molecular pathology of endometrial carcinoma: practical aspects from the diagnostic and therapeutic viewpoints
J. Clin. Pathol., September 1, 2009; 62(9): 777 - 785.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Maurer, T. Su, L. H. Saal, S. Koujak, B. D. Hopkins, C. R. Barkley, J. Wu, S. Nandula, B. Dutta, Y. Xie, et al.
3-Phosphoinositide-Dependent Kinase 1 Potentiates Upstream Lesions on the Phosphatidylinositol 3-Kinase Pathway in Breast Carcinoma
Cancer Res., August 1, 2009; 69(15): 6299 - 6306.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
P. Sabbatini and D. R. Spriggs
Epothilones: Better or More of the Same?
J. Clin. Oncol., July 1, 2009; 27(19): 3079 - 3081.
[Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
P. Chaudhry and E. Asselin
Resistance to chemotherapy and hormone therapy in endometrial cancer
Endocr. Relat. Cancer, June 1, 2009; 16(2): 363 - 380.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. B. Salvesen, S. L. Carter, M. Mannelqvist, A. Dutt, G. Getz, I. M. Stefansson, M. B. Raeder, M. L. Sos, I. B. Engelsen, J. Trovik, et al.
Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation
PNAS, March 24, 2009; 106(12): 4834 - 4839.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. T. Ihle, R. Lemos Jr., P. Wipf, A. Yacoub, C. Mitchell, D. Siwak, G. B. Mills, P. Dent, D. L. Kirkpatrick, and G. Powis
Mutations in the Phosphatidylinositol-3-Kinase Pathway Predict for Antitumor Activity of the Inhibitor PX-866 whereas Oncogenic Ras Is a Dominant Predictor for Resistance
Cancer Res., January 1, 2009; 69(1): 143 - 150.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
U. Banerji
Heat Shock Protein 90 as a Drug Target: Some Like It Hot
Clin. Cancer Res., January 1, 2009; 15(1): 9 - 14.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
F. Perrone, A. Lampis, M. Orsenigo, M. Di Bartolomeo, A. Gevorgyan, M. Losa, M. Frattini, C. Riva, S. Andreola, E. Bajetta, et al.
PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients
Ann. Onc., January 1, 2009; 20(1): 84 - 90.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Szabolcs, M. Keniry, L. Simpson, L. J. Reid, S. Koujak, S. C. Schiff, G. Davidian, S. Licata, S. Gruvberger-Saal, V. V.V.S. Murty, et al.
Irs2 Inactivation Suppresses Tumor Progression in Pten+/- Mice
Am. J. Pathol., January 1, 2009; 174(1): 276 - 286.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Oda, J. Okada, L. Timmerman, P. Rodriguez-Viciana, D. Stokoe, K. Shoji, Y. Taketani, H. Kuramoto, Z. A. Knight, K. M. Shokat, et al.
PIK3CA Cooperates with Other Phosphatidylinositol 3'-Kinase Pathway Mutations to Effect Oncogenic Transformation
Cancer Res., October 1, 2008; 68(19): 8127 - 8136.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Wee, D. Wiederschain, S.-M. Maira, A. Loo, C. Miller, R. deBeaumont, F. Stegmeier, Y.-M. Yao, and C. Lengauer
PTEN-deficient cancers depend on PIK3CB
PNAS, September 2, 2008; 105(35): 13057 - 13062.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
V. E. Velculescu
Defining the blueprint of the cancer genome
Carcinogenesis, June 1, 2008; 29(6): 1087 - 1091.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. H. Lu, W. Wu, B. Dave, B. M. Slomovitz, T. W. Burke, M. F. Munsell, R. R. Broaddus, and C. L. Walker
Loss of Tuberous Sclerosis Complex-2 Function and Activation of Mammalian Target of Rapamycin Signaling in Endometrial Carcinoma
Clin. Cancer Res., May 1, 2008; 14(9): 2543 - 2550.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
I. Opitz, A. Soltermann, M. Abaecherli, M. Hinterberger, N. Probst-Hensch, R. Stahel, H. Moch, and W. Weder
PTEN expression is a strong predictor of survival in mesothelioma patients
Eur. J. Cardiothorac. Surg., March 1, 2008; 33(3): 502 - 506.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Andres-Pons, I. Rodriguez-Escudero, A. Gil, A. Blanco, A. Vega, M. Molina, R. Pulido, and V. J. Cid
In vivo Functional Analysis of the Counterbalance of Hyperactive Phosphatidylinositol 3-Kinase p110 Catalytic Oncoproteins by the Tumor Suppressor PTEN
Cancer Res., October 15, 2007; 67(20): 9731 - 9739.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Perez-Tenorio, L. Alkhori, B. Olsson, M. A. Waltersson, B. Nordenskjold, L. E. Rutqvist, L. Skoog, and O. Stal
PIK3CA Mutations and PTEN Loss Correlate with Similar Prognostic Factors and Are Not Mutually Exclusive in Breast Cancer
Clin. Cancer Res., June 15, 2007; 13(12): 3577 - 3584.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. H. Saal, P. Johansson, K. Holm, S. K. Gruvberger-Saal, Q.-B. She, M. Maurer, S. Koujak, A. A. Ferrando, P. Malmstrom, L. Memeo, et al.
Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity
PNAS, May 1, 2007; 104(18): 7564 - 7569.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Moreno-Bueno, P. J. Fernandez-Marcos, M. Collado, M. J. Tendero, S. M. Rodriguez-Pinilla, I. Garcia-Cao, D. Hardisson, M. T. Diaz-Meco, J. Moscat, M. Serrano, et al.
Inactivation of the Candidate Tumor Suppressor Par-4 in Endometrial Cancer
Cancer Res., March 1, 2007; 67(5): 1927 - 1934.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. P. Hayes, H. Wang, R. Espinal-Witter, W. Douglas, G. J. Solomon, S. J. Baker, and L. H. Ellenson
PIK3CA and PTEN Mutations in Uterine Endometrioid Carcinoma and Complex Atypical Hyperplasia.
Clin. Cancer Res., October 15, 2006; 12(20): 5932 - 5935.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. L. Hecht and G. L. Mutter
Molecular and Pathologic Aspects of Endometrial Carcinogenesis
J. Clin. Oncol., October 10, 2006; 24(29): 4783 - 4791.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
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.
PIK3CA Gene Mutations in Pediatric and Adult Glioblastoma Multiforme
Mol. Cancer Res., October 1, 2006; 4(10): 709 - 714.
[Abstract] [Full Text] [PDF]

Home page
 Cold Spring Harb Symp Quant BiolHome page
P. RODRIGUEZ-VICIANA, O. TETSU, K. ODA, J. OKADA, K. RAUEN, and F. McCORMICK
Cancer Targets in the Ras Pathway
Cold Spring Harb Symp Quant Biol, January 1, 2005; 70(0): 461 - 467.
[Abstract] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2005 by the American Association for Cancer Research.