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[Cancer Research 57, 4997-5000, November 15, 1997]
© 1997 American Association for Cancer Research
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Frequent Inactivation of PTEN/MMAC1 in Primary Prostate Cancer

Paul Cairns, Kenji Okami, Sarel Halachmi, Naomi Halachmi, Manel Esteller, James G. Herman, Jin Jen, W. B. Isaacs, G. Steven Bova and David Sidransky1

Head and Neck Cancer Research, Department of Otolaryngology [P. C., K. O., S. H., N. H., J. J., D. S.], Oncology Center [M. E., J. G. H., W. B. I., D. S.], Departments of Urology [W. B. I.] and Pathology [G. S. B.], Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Sporadic prostate carcinoma is the most common male cancer in the Western world, yet many of the major genetic events involved in the progression of this often fatal cancer remain to be elucidated. Numerous cytogenetic and allelotype studies have reported frequent loss of heterozygosity on chromosomal arm 10q in sporadic prostate cancer. Deletion mapping studies have unambiguously identified a region of chromosome 10q23 to be the minimal area of loss. A new tumor suppressor gene, PTEN/MMAC1, was isolated recently at this region of chromosome 10q23 and found to be inactivated by mutation in three prostate cancer cell lines. We screened 80 prostate tumors by microsatellite analysis and found chromosome 10q23 to be deleted in 23 cases. We then proceeded with sequence analysis of the entire PTEN/MMAC1 coding region and tested for homozygous deletion with new intragenic markers in these 23 cases with 10q23 loss of heterozygosity. The identification of the second mutational event in 10 (43%) tumors establishes PTEN/MMAC1 as a main inactivation target of 10q loss in sporadic prostate cancer.

1 To whom requests for reprints should be addressed, at Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, 818 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205-2196.

Received 9/12/97. Accepted 10/ 2/97.




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Am. J. Pathol., October 1, 2000; 157(4): 1123 - 1128.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
H. Kato, S. Kato, T. Kumabe, Y. Sonoda, T. Yoshimoto, S. Kato, S.-Y. Han, T. Suzuki, H. Shibata, R. Kanamaru, et al.
Functional Evaluation of p53 and PTEN Gene Mutations in Gliomas
Clin. Cancer Res., October 1, 2000; 6(10): 3937 - 3943.
[Abstract] [Full Text]

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 Am. J. Respir. Cell Mol. Bio.Home page
T.-M. Hong, P.-C. Yang, K. Peck, J. J. W. Chen, S.-C. Yang, Y.-C. Chen, and C.-W. Wu
Profiling the Downstream Genes of Tumor Suppressor PTEN in Lung Cancer Cells by Complementary DNA Microarray
Am. J. Respir. Cell Mol. Biol., September 1, 2000; 23(3): 355 - 363.
[Abstract] [Full Text]

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J. T. Çelebi, I. Shendrik, D. N Silvers, and M. Peacocke
Identification of PTEN mutations in metastatic melanoma specimens
J. Med. Genet., September 1, 2000; 37(9): 653 - 657.
[Abstract] [Full Text]

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 Clin. Cancer Res.Home page
G. L. Maxwell, J. I. Risinger, K. A. Hayes, A. A. Alvarez, R. K. Dodge, J. C. Barrett, and A. Berchuck
Racial Disparity in the Frequency of PTEN Mutations, but not Microsatellite Instability, in Advanced Endometrial Cancers
Clin. Cancer Res., August 1, 2000; 6(8): 2999 - 3005.
[Abstract] [Full Text]

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 Clin. Cancer Res.Home page
A. H. Holway, K. M. Rieger-Christ, W. R. Miner, J. W. Cain, J. M. Dugan, J. A. Pezza, M. L. Silverman, A. Shapter, R. McLellan, and I. C. Summerhayes
Somatic Mutation of PTEN in Vulvar Cancer
Clin. Cancer Res., August 1, 2000; 6(8): 3228 - 3235.
[Abstract] [Full Text]

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 Hum Mol GenetHome page
O. Gimm, T. Attie-Bitach, J. A. Lees, M. Vekemans, and C. Eng
Expression of the PTEN tumour suppressor protein during human development
Hum. Mol. Genet., July 1, 2000; 9(11): 1633 - 1639.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
V. Stambolic, M.-S. Tsao, D. Macpherson, A. Suzuki, W. B. Chapman, and T. W. Mak
High Incidence of Breast and Endometrial Neoplasia Resembling Human Cowden Syndrome in pten+/- Mice
Cancer Res., July 1, 2000; 60(13): 3605 - 3611.
[Abstract] [Full Text]

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 Cancer Res.Home page
S.-Y. Han, H. Kato, S. Kato, T. Suzuki, H. Shibata, S. Ishii, K.-i. Shiiba, S. Matsuno, R. Kanamaru, and C. Ishioka
Functional Evaluation of PTEN Missense Mutations Using in Vitro Phosphoinositide Phosphatase Assay
Cancer Res., June 1, 2000; 60(12): 3147 - 3151.
[Abstract] [Full Text]

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I. De Vivo, D. M Gertig, S. Nagase, S. E Hankinson, R. O'Brien, F. E Speizer, R. Parsons, and D. J Hunter
Novel germline mutations in the PTEN tumour suppressor gene found in women with multiple cancers
J. Med. Genet., May 1, 2000; 37(5): 336 - 341.
[Abstract] [Full Text]

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 Am. J. Pathol.Home page
O. Gimm, A. Perren, L.-P. Weng, D. J. Marsh, J. J. Yeh, U. Ziebold, E. Gil, R. Hinze, L. Delbridge, J. A. Lees, et al.
Differential Nuclear and Cytoplasmic Expression of PTEN in Normal Thyroid Tissue, and Benign and Malignant Epithelial Thyroid Tumors
Am. J. Pathol., May 1, 2000; 156(5): 1693 - 1700.
[Abstract] [Full Text] [PDF]

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 BloodHome page
J. J. Scarisbrick, A. J. Woolford, R. Russell-Jones, and S. J. Whittaker
Loss of heterozygosity on 10q and microsatellite instability in advanced stages of primary cutaneous T-cell lymphoma and possible association with homozygous deletion of PTEN
Blood, May 1, 2000; 95(9): 2937 - 2942.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
P. Zhang and B. M. Steinberg
Overexpression of PTEN/MMAC1 and Decreased Activation of Akt in Human Papillomavirus-infected Laryngeal Papillomas
Cancer Res., March 1, 2000; 60(5): 1457 - 1462.
[Abstract] [Full Text]

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M. S FORREST, S. M EDWARDS, R. A HAMOUDI, D. P DEARNALEY, A. ARDEN-JONES, A. DOWE, A. MURKIN, J. KELLY, M D. TEARE, D. F EASTON, et al.
No evidence of germline PTEN mutations in familial prostate cancer
J. Med. Genet., March 1, 2000; 37(3): 210 - 212.
[Full Text]

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 JNCI J Natl Cancer InstHome page
I. U. Ali, L. M. Schriml, and M. Dean
Mutational Spectra of PTEN/MMAC1 Gene: a Tumor Suppressor With Lipid Phosphatase Activity
J Natl Cancer Inst, November 17, 1999; 91(22): 1922 - 1932.
[Abstract] [Full Text] [PDF]

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 JNCI J Natl Cancer InstHome page
M. Tamura, J. Gu, H. Tran, and K. M. Yamada
PTEN Gene and Integrin Signaling in Cancer
J Natl Cancer Inst, November 3, 1999; 91(21): 1820 - 1828.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
A. Chott, Z. Sun, D. Morganstern, J. Pan, T. Li, M. Susani, I. Mosberger, M. P. Upton, G. J. Bubley, and S. P. Balk
Tyrosine Kinases Expressed in Vivo by Human Prostate Cancer Bone Marrow Metastases and Loss of the Type 1 Insulin-Like Growth Factor Receptor
Am. J. Pathol., October 1, 1999; 155(4): 1271 - 1279.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
M. E. McMenamin, P. Soung, S. Perera, I. Kaplan, M. Loda, and W. R. Sellers
Loss of PTEN Expression in Paraffin-embedded Primary Prostate Cancer Correlates with High Gleason Score and Advanced Stage
Cancer Res., September 1, 1999; 59(17): 4291 - 4296.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
M. Hahn, I. Wieland, O. N. Koufaki, H. Gorgens, S. B. Sobottka, G. Schackert, and H. K. Schackert
Genetic Alterations of the Tumor Suppressor Gene PTEN/MMAC1 in Human Brain Metastases
Clin. Cancer Res., September 1, 1999; 5(9): 2431 - 2437.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
M.-M. Georgescu, K. H. Kirsch, T. Akagi, T. Shishido, and H. Hanafusa
The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region
PNAS, August 31, 1999; 96(18): 10182 - 10187.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
H. Fujisawa, M. Kurrer, R. M. Reis, Y. Yonekawa, P. Kleihues, and H. Ohgaki
Acquisition of the Glioblastoma Phenotype during Astrocytoma Progression Is Associated with Loss of Heterozygosity on 10q25-qter
Am. J. Pathol., August 1, 1999; 155(2): 387 - 394.
[Abstract] [Full Text] [PDF]

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M. Tamura, J. Gu, E. H. J. Danen, T. Takino, S. Miyamoto, and K. M. Yamada
PTEN Interactions with Focal Adhesion Kinase and Suppression of the Extracellular Matrix-dependent Phosphatidylinositol 3-Kinase/Akt Cell Survival Pathway
J. Biol. Chem., July 16, 1999; 274(29): 20693 - 20703.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
M. A. Davies, D. Koul, H. Dhesi, R. Berman, T. J. McDonnell, D. McConkey, W. K. A. Yung, and P. A. Steck
Regulation of Akt/PKB Activity, Cellular Growth, and Apoptosis in Prostate Carcinoma Cells by MMAC/PTEN
Cancer Res., June 1, 1999; 59(11): 2551 - 2556.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
K. A. Cooney, H. C. Tsou, E. M. Petty, S. Miesfeldt, X. L. Ping, A. C. Gruener, and M. Peacocke
Absence of PTEN Germ-Line Mutations in Men with a Potential Inherited Predisposition to Prostate Cancer
Clin. Cancer Res., June 1, 1999; 5(6): 1387 - 1391.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
H. Sun, R. Lesche, D.-M. Li, J. Liliental, H. Zhang, J. Gao, N. Gavrilova, B. Mueller, X. Liu, and H. Wu
PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway
PNAS, May 25, 1999; 96(11): 6199 - 6204.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
L. C. Cantley and B. G. Neel
New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway
PNAS, April 13, 1999; 96(8): 4240 - 4245.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
T. Sano, H. Lin, X. Chen, L. A. Langford, D. Koul, M. L. Bondy, K. R. Hess, J. N. Myers, Y.-K. Hong, W. K. A. Yung, et al.
Differential Expression of MMAC/PTEN in Glioblastoma Multiforme: Relationship to Localization and Prognosis
Cancer Res., April 1, 1999; 59(8): 1820 - 1824.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
S. Ramaswamy, N. Nakamura, F. Vazquez, D. B. Batt, S. Perera, T. M. Roberts, and W. R. Sellers
Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway
PNAS, March 2, 1999; 96(5): 2110 - 2115.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
K. Podsypanina, L. H. Ellenson, A. Nemes, J. Gu, M. Tamura, K. M. Yamada, C. Cordon-Cardo, G. Catoretti, P. E. Fisher, and R. Parsons
Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems
PNAS, February 16, 1999; 96(4): 1563 - 1568.
[Abstract] [Full Text] [PDF]

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 Endocr. Rev.Home page
E. Ruijter, C. van de Kaa, G. Miller, D. Ruiter, F. Debruyne, and J. Schalken
Molecular Genetics and Epidemiology of Prostate Carcinoma
Endocr. Rev., February 1, 1999; 20(1): 22 - 45.
[Abstract] [Full Text]

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 DevelopmentHome page
H Huang, C. Potter, W Tao, D. Li, W Brogiolo, E Hafen, H Sun, and T Xu
PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development
Development, January 12, 1999; 126(23): 5365 - 5372.
[Abstract] [PDF]

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 Cancer Res.Home page
M. Tamura, J. Gu, T. Takino, and K. M. Yamada
Tumor Suppressor PTEN Inhibition of Cell Invasion, Migration, and Growth: Differential Involvement of Focal Adhesion Kinase and p130Cas
Cancer Res., January 1, 1999; 59(2): 442 - 449.
[Abstract] [Full Text] [PDF]

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 Genes Dev.Home page
L. Chin, G. Merlino, and R. A. DePinho
Malignant melanoma: modern black plague and genetic black box
Genes & Dev., November 15, 1998; 12(22): 3467 - 3481.
[Full Text]

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 Proc. Natl. Acad. Sci. USAHome page
M. P. Myers, I. Pass, I. H. Batty, J. Van der Kaay, J. P. Stolarov, B. A. Hemmings, M. H. Wigler, C. P. Downes, and N. K. Tonks
The lipid phosphatase activity of PTEN is critical for its tumor supressor function
PNAS, November 10, 1998; 95(23): 13513 - 13518.
[Abstract] [Full Text] [PDF]


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