Abstract
A putative tumor suppressor, the PTEN gene at chromosome 10q23, was identified and found to be mutated in many different human tumors. PTEN was recently found to be also involved in focal cell adhesion and cell migration. To identify the role of PTEN gene in malignant gliomas, we used PCR-SSCP and direct sequencing methods to examine 44 malignant gliomas comprising 29 cases without and 15 cases with meningeal gliomatosis. In malignant gliomas without meningeal gliomatosis, 2/29 (7%) of the cases showed alteration of the PTEN gene. In contrast, 5/15 (33%) of malignant gliomas with meningeal gliomatosis cases showed this alteration. These findings indicate that PTEN gene mutation contributes not only to the neoplastic evolution in gliomas but also to the meningeal dissemination of glioma cells.
Similar content being viewed by others
References
Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanell BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1943–1947, 1997
Steck PA, Pershouse MA, Jasser SA, Yung WKA, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DHF, Tavtigian SV: Identification of a candidate tumour suppressor gene,MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nature Genet 15: 356–362, 1997
Knudson AG Jr, Hethcote HW, Brown BW: Mutation and childhood cancer. Proc Natl Acad Sci USA 72: 5116–5120, 1975
Maier D, Zhang Z, Taylor E, Hamou M-F, Gratzl O, Van Meir EG, Scott RJ, Merlo A: Somatic deletion mapping on chromosome 10 and sequence analysis of PTEN/MMAC1 point to the 10q25-26 region as the primary target in low-grade and high-grade gliomas. Oncogene 16: 3331–3335, 1998
Duerr E-M, Rollbrocker B, Hayashi Y, Peters N, Merer-Puttlitz B, Louis DN, Schramm J, Wiestler OD, Parsons R, Eng C, von Deimling A: PTEN mutations in gliomas and glioneuronal tumors. Oncogene 16: 2259–2264, 1998
Rasheed BKA, Stenzel TT, McLendon RE, Parsons R, Friedman AH, Friedman HS, Bigner DD, Bigner SH: PTEN gene mutations are seen in high-grade but not in low-grade gliomas. Cancer Res 57: 4187–4190, 1997
Bostrom J, Cobbers JMJL, Wolter M, Tabatabai G, Weber RG, Lichter P, Collins VP, Reifenberger G: Mutation of the PTEN (MMAC1) tumor suppressor gene in a subset of glioblastomas but not in meningiomas with loss of chromosome arm 10q. Cancer Res 58: 29–33, 1998
Wang SI, Puc J, Li J, Bruce JN, Cairns P, Sidransky D, Parsons R: Somatic mutations ofPTENin glioblastoma multiforme. Cancer Res 57: 4183–4186, 1997
Zhou X-P, Li Y-J, Hoang-Xuan K, Laurent-Puig P, Mokhtari K, Longy M, Sanson M, Delattre J-Y, Thomas G, Hamelin R: Mutational analysis of the PTEN gene in gliomas: molecular and pathological correlations. Int J Cancer 84: 150–154, 1999
Schmidt EE, Ichimura K, Goike HM, Moshref A, Liu L, Collins VP: Mutational profile of the PTEN gene in primary human astrocytic tumors and cultivated xenografts. J Neuropath Exp Neurol 58: 1170–1183, 1999
Somerville RPT, Shoshan Y, Eng C, Barnett G, Miller D, Cowell JK: Molecular analysis of two putative tumour suppressor genes, PTEN and DMBT, which have been implicated in glioblastoma multiforme disease progression. Oncogene 17: 1755–1757, 1998
Sakurada A, Suzuki A, Sato M, Yamakawa H, Orikasa K, Uyeno S, Ono T, Ohuchi N, Fujimura S, Horii A: Infrequent genetic alterations of the PTEN/MMAC1 gene in Japanese patients with primary cancers of the breast, lung, pancreas, kidney, and ovary. Jpn J Cancer Res 88: 1025–1028, 1997
Ueda K, Nishijima M, Inui H, Watatani M, Yayoi E, Okamura J, Yasutomi M, Nakamura Y, Miyoshi Y: Infrequent mutations in the PTEN/MMAC1 gene among primary breast cancers. Jpn J Cancer Res 89: 17–21, 1998
Mollenhauer J, Wiemann S, Scheurlen W, Korn B, Hayashi Y, Wilgenbus KK, von Deimling A, Poustka A: DMBT1, a new member of the SRCR superfamily of chromosome 10q25.3-26.1 is deleted in malignant brain tumours. Nature Genet 17: 32–39, 1997
Adachi J, Ohbayashi K, Suzuki T, Sasaki T: Cell cycle arrest and astrocytic differentiation resulting from PTEN expression in glioma cells. J Neurosurg 91: 822–830, 1999
Furnari FB, Lin H, Huang H-JS, Cavenee WK: Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain. Proc Natl Acad Sci USA 94: 12479–12484, 1997
Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, Ruland J, Penninger JM, Siderovski DP, Mak TW: Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95: 29–39, 1998
Lo SH, Weisberg E, Chen LB: Tensin: a potential link between the cytoskeleton and signal transduction. Bioessays 16: 817–823, 1994
Tamura M, Gu J, Matsumoto K, Aota S, Parsons R, Yamada KM: Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 280, 1614–1617, 1998
Tamura M, Gu J, Takino T, Yamada KM: Tumor suppressor PTEN inhibition of cell invasion, migration, and growth: differential involvement of focal adhesion kinase and p130Cas. Cancer Res 59: 442–449, 1999
Maier D, Jones G, Li X, Schonthal AH, Gratzl O, Van Meir FG, Merlo A: ThePTEN lipid phosphatase domain is not required to inhibit invasion of glioma cells. Cancer Res 59: 5479–5482, 1999
Cheney IW, Johnson DE, Vaillancourt M-T, Avanzini J, Morimoto A, Demers GW, Wills KN, Shabram PW, Bolen JB, Tavtigian SV, Bookstein R: Suppression of tumorigenicity of glioblastoma cells by adenovirusmediated MMAC1/PTEN gene transfer. Cancer Res 58: 2331–2334, 1998
Di Cristofano A, Pesce B, Cordon-Cardo C, Pandolfi PP: Pten is essential for embryonic development and tumour suppression. Nature Genet 19: 348–3355, 1998
Arita N, Taneda M, Hayakawa T: Leptomeningeal dissemination of malignant gliomas. Acta Neurochir (Wien) 126: 84–92, 1994
Oto M, Miyake S, Yuasa Y: Optimization of nonradioisotopic single strand conformation polymorphism analysis with a conventional minislab gel electrophoresis apparatus. Analytical Biochem 213: 19–22, 1993
Grant R, Naylor B, Junck L, Greenberg HS: Clinical outcome in aggressively treated meningeal gliomatosis. Neurology 42: 252–254, 1992
Kong D, Suzuki A Zou T-T, Sakurada A, Kemp LW, Wakatsuki S, Yokoyama T, Yamakawa H, Furukawa T, Sato M, Ohuchi N, Sato S, Yin J, Wang S, Abraham JM, Souza R, Smolinski KN, Meltzer SJ, Horii A: PTEN1 is frequently mutated in primary endometrial carcinomas. Nature Genet 17: 143–144, 1997
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Izumoto, S., Ohnishi, T., Kanemura, H. et al. PTEN Mutations in Malignant Gliomas and their Relation with Meningeal Gliomatosis. J Neurooncol 53, 21–26 (2001). https://doi.org/10.1023/A:1011839920176
Issue Date:
DOI: https://doi.org/10.1023/A:1011839920176