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Department of Tumor Cell Biology, Division of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen Ø, [P. G., P. t. S., A. B., V. A., A. F. K., J. Z.]; and Department of Pathology, Rigshospitalet, DK-2100 Copenhagen Ø [A. B.], Denmark
The MMAC1/PTEN gene, located at 10q23.3, is a candidate tumor suppressor commonly mutated in glioma. We have studied the pattern of deletion, mutation, and expression of MMAC1/PTEN in 35 unrelated melanoma cell lines. Nine (26%) of the cell lines showed partial or complete homozygous deletion of the MMAC1/PTEN gene, and another six (17%) harbored a mutation in combination with loss of the second allele. Mutations could also be demonstrated in uncultured tumor specimens from which the cell lines had been established, and cell lines derived from two different metastases from one individual carried the same missense mutation. Collectively, these findings suggest that disruption of MMAC1/PTEN by allelic loss or mutation may contribute to the pathogenesis or neoplastic evolution in a large proportion of malignant melanomas.
1 This work was supported by grants from the Danish Cancer Society, the Danish Medical Research Council, and the Novo Nordisk Foundation.
2 To whom requests for reprints should be addressed, at the Department of Tumor Cell Biology, Division of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark.
Received 6/24/97. Accepted 7/18/97.
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G. P. Robertson, R. A. Herbst, M. Nagane, H-J. S. Huang, and W. K. Cavenee The Chromosome 10 Monosomy Common in Human Melanomas Results from the Loss of Two Separate Tumor Suppressor Loci Cancer Res., August 1, 1999; 59(15): 3596 - 3601. [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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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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 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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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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E. B. Gil, E. Malone Link, L. X. Liu, C. D. Johnson, and J. A. Lees Regulation of the insulin-like developmental pathway of Caenorhabditis elegans by a homolog of the PTEN tumor suppressor gene PNAS, March 16, 1999; 96(6): 2925 - 2930. [Abstract] [Full Text] [PDF]
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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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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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 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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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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 R. Siebert, S. Gesk, S. Harder, S. Plotz, P. Matthiesen, W. Grote, B. Schlegelberger, B. Jandrig, U.-H. Grasmo-Wendler, S. Scherneck, et al. Deletions in the Long Arm of Chromosome 10 in Lymphomas With t(14;18): A Pathogenetic Role of the Tumor Suppressor Genes PTEN/MMAC1 and MXI1? Blood, December 1, 1998; 92(11): 4487 - 4489. [Full Text] [PDF]
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 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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A. Sakai, C. Thieblemont, A. Wellmann, E. S. Jaffe, and M. Raffeld PTEN Gene Alterations in Lymphoid Neoplasms Blood, November 1, 1998; 92(9): 3410 - 3415. [Abstract] [Full Text] [PDF]
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G. P. Robertson, F. B. Furnari, M. E. Miele, M. J. Glendening, D. R. Welch, J. W. Fountain, T. G. Lugo, H.-J. S. Huang, and W. K. Cavenee In vitro loss of heterozygosity targets the PTEN/MMAC1 gene in melanoma PNAS, August 4, 1998; 95(16): 9418 - 9423. [Abstract] [Full Text] [PDF]
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Z.-J. Wang, F. Taylor, M. Churchman, G. Norbury, and I. Tomlinson Genetic Pathways of Colorectal Carcinogenesis Rarely Involve the PTEN and LKB1 Genes Outside the Inherited Hamartoma Syndromes Am. J. Pathol., August 1, 1998; 153(2): 363 - 366. [Abstract] [Full Text] [PDF]
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 M. Tamura, J. Gu, K. Matsumoto, S. Aota, R. Parsons, and K. M. Yamada Inhibition of Cell Migration, Spreading, and Focal Adhesions by Tumor Suppressor PTEN Science, June 5, 1998; 280(5369): 1614 - 1617. [Abstract] [Full Text]
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K. Gronbak, J. Zeuthen, P. Guldberg, E. Ralfkiar, and K. Hou-Jensen Alterations of the MMAC1/PTEN Gene in Lymphoid Malignancies Blood, June 1, 1998; 91(11): 4388 - 4390. [Full Text] [PDF]
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Y. E. Whang, X. Wu, H. Suzuki, R. E. Reiter, C. Tran, R. L. Vessella, J. W. Said, W. B. Isaacs, and C. L. Sawyers Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression PNAS, April 28, 1998; 95(9): 5246 - 5250. [Abstract] [Full Text] [PDF]
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S. Persad, S. Attwell, V. Gray, M. Delcommenne, A. Troussard, J. Sanghera, and S. Dedhar Inhibition of integrin-linked kinase (ILK) suppresses activation of protein kinase B/Akt and induces cell cycle arrest and apoptosis of PTEN-mutant prostate cancer cells PNAS, March 28, 2000; 97(7): 3207 - 3212. [Abstract] [Full Text] [PDF]
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 L. Kotelevets, J. van Hengel, E. Bruyneel, M. Mareel, F. van Roy, and E. Chastre The lipid phosphatase activity of PTEN is critical for stabilizing intercellular junctions and reverting invasiveness J. Cell Biol., December 24, 2001; 155(7): 1129 - 1136. [Abstract] [Full Text] [PDF]
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