Home Duke University Press
 QUICK SEARCH:   [advanced]


     
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents


Neuro Oncol 1999 1(1):44-51; DOI:10.1215/15228517-1-1-44
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
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 Kleihues, P.
Right arrow Articles by Ohgaki, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Duke University Press

Symposium Genetic Classification and Treatment of Malignant Gliomas and Oligodendrogliomas

Primary and secondary glioblastomas: From concept to clinical diagnosis

Paul Kleihues2 and Hiroko Ohgaki

International Agency for Research on Cancer (IARC), World Health Organization (WHO), Lyon, France

2 Address correspondence and reprint requests to Dr. Paul Kleihues, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon, France.

Abstract

Glioblastomas may develop de novo (primary glioblastomas) or through progression from low-grade or anaplastic astrocytomas (secondary glioblastomas). These subtypes of glioblastoma constitute distinct disease entities that evolve through different genetic pathways, affect patients at different ages, and are likely to differ in prognosis and response to therapy. Primary glioblastomas develop in older patients and typically show EGFR overexpression, PTEN (MMAC1) mutations, CDKN2A (p16) deletions, and less frequently, MDM2 amplification. Secondary glioblastomas develop in younger patients and often contain TP53 mutations as the earliest detectable alteration. These characteristics are derived largely from patients selected on the basis of clinical history and sequential biopsies. Currently available data are insufficient for a substitution of histologic classification and grading of astrocytic tumors by genetic typing alone. More subtypes of glioblastomas may exist with intermediate clinical and genetic profiles, a factor exemplified by the giant-cell glioblastoma that clinically and genetically occupies a hybrid position between primary (de novo) and secondary glioblastomas. Future research should aim at the identification of criteria for a combined clinical, histologic, and genetic classification of astrocytic tumors.

References

al-Sarraj, S., and Bridges, L.R. (1995) p53 immunoreactivity in astrocytomas and its relationship to survival. Br. J. Neurosurg. 9,143 -149.[CrossRef][ISI][Medline]

Albarosa, R., Colombo, B.M., Roz, L., Magnani, I., Pollo, B., Cirenei, N., Giani, C., Conti, A.M., DiDonato, S., and Finocchiaro, G. (1996) Deletion mapping of gliomas suggest the presence of two small regions for candidate tumor-suppressor genes in a 17-cM interval on chromosome 10q. Am. J. Hum. Genet. 58,1260 -1267.[ISI][Medline]

Ashley, D.M., and Bigner, D.D. (1997) Recent advances in the biology of central nervous system tumors. Curr. Opin. Neurol. 10,445 -451.[ISI][Medline]

Barak, Y., Gottlieb, E., Juven-Gershon, T., and Oren, M. (1994) Regulation of mdm2 expression by p53: Alternative promoters produce transcripts with nonidentical translation potential. Genes Dev. 8,1739 -1749.[Abstract/Free Full Text]

Barker, F.G., II, Davis, R.L., Chang, S.M., and Prados, M.D. (1996) Necrosis as a prognostic factor in glioblastoma multiforme. Cancer 77,1161 -1166.[CrossRef][ISI][Medline]

Biernat, W., Kleihues, P., Yonekawa, Y., and Ohgaki, H. (1997a) Amplification and overexpression of MDM2 in primary (de novo) glioblastomas. J. Neuropathol. Exp. Neurol. 56,180 -185.[ISI][Medline]

Biernat, W., Tohma, Y., Yonekawa, Y., Kleihues, P., and Ohgaki, H. (1997b) Alterations of cell cycle regulatory genes in primary (de novo) and secondary glioblastomas. Acta. Neuropathol. 94,303 -309.[CrossRef][Medline]

Bostrom, J., Cobbers, J.M.J.L., Wolter, M., Tabatabai, G., Weber, R.G., Lichter, P., Collins, V.P., and Reifenberger, G. (1998) Mutation of the PTEN (MMAC1) tumor suppressor gene in a subset of glioblastomas but not in meningiomas with loss of chromosome arm 10q1. Cancer Res. 58, 29-33.[Abstract/Free Full Text]

Burger, P.C., and Green, S.B. (1987) Patient age, histologic features, and length of survival in patients with glioblastoma multiforme. Cancer 59,1617 -1625.[CrossRef][ISI][Medline]

Burger, P.C., and Kleihues, P. (1989) Cytologic composition of the untreated glioblastoma with implications for evaluation of needle biopsies. Cancer 63,2014 -2023.[CrossRef][ISI][Medline]

Burger, P.C., and Scheithauer, B.W. (1994) Tumors of the Central Nervous System. Atlas of tumor pathology, third series, fascicle 10. Washington: Armed Forces Institute of Pathology.

Burns, K.L., Ueki, K., Jhung, S.L., Koh, J., and Louis, D.N. (1998) Molecular genetic correlates of p16, cdk4, and pRb immunohistochemistry in glioblastomas. J. Neuropathol. Exp. Neurol. 57,122 -130.[ISI][Medline]

Claesson Welsh, L. (1994) Platelet-derived growth factor receptor signals. J. Biol. Chem. 269,32023 -32026.[Free Full Text]

Collins, V.P. (1995) Gene amplification in human gliomas. Glia 15,289 -296.[CrossRef][ISI][Medline]

Dirks, P.B., and Rutka, J.T. (1997) Current concepts in neuro-oncology: The cell cycle—a review. Neurosurgery 40,1000 -1013.[ISI][Medline]

Dropcho, E.J., and Soong, S.J. (1996) The prognostic impact of prior low grade histology in patients with anaplastic gliomas: A case-control study. Neurology 47,684 -690.[Abstract/Free Full Text]

Duerr, E.-M., Rollbrocker, B., Hayashi, Y., Peters, N., Meyer-Puttlitz, B., Louis, D.N., Schramm, J., Wiestler, O.D., Parsons, R., Eng, C., and von Deimling, A. (1998) PTEN mutations in gliomas and glioneuronal tumors. Oncogene 16,2259 -2264.[CrossRef][ISI][Medline]

Ekstrand, A.J., Sugawa, N., James, C.D., and Collins, V.P. (1992) Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. Proc. Natl. Acad. Sci. U. S. A. 89,4309 -4313.[Abstract/Free Full Text]

Fearon, E.R., Cho, K.R., Nigro, J.M., Kern, S.E., Simons, J.W., Ruppert, J.M., Hamilton, S.R., Preisinger, A.C., Thomas, G., Kinzler, K.W., Kinzler, K.W., and Vogelstein, B. (1990) Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247,49 -56.[Abstract/Free Full Text]

Fults, D., and Pedone, C. (1993) Deletion mapping of the long arm of chromosome 10 in glioblastoma multiforme. Genes Chromosom. Cancer 7,173 -177.[ISI][Medline]

Haffner, R., and Oren, M. (1995) Biochemical properties and biological effects of p53. Curr. Opin. Genet. Dev. 5,84 -90.[CrossRef][Medline]

Hainaut, P. (1995) The tumor suppressor protein p53: A receptor to genotoxic stress that controls cell growth and survival. Curr. Opin. Oncol. 7,76 -82.[Medline]

Hayashi, Y., Ueki, K., Waha, A., Wiestler, O.D., Louis, D.N., and von Deimling, A. (1997) Association of EGFR gene amplification and CDKN2 (p16/MTS1) gene deletion in glioblastoma multiforme. Brain Pathol. 7, 871-875.[ISI][Medline]

Heldin, C.H., and Westermark, B. (1990) Platelet-derived growth factor: Mechanism of action and possible in vivo function. Cell Regul. 1,555 -566.[ISI][Medline]

Hermanson, M., Funa, K., Koopmann, J., Maintz, D., Waha, A., Westermark, B., Heldin, C.H., Wiestler, O.D., Louis, D.N., von Deimling, A., and Nister, M. (1996) Association of loss of heterozygosity on chromosome 17p with high platelet-derived growth factor alpha receptor expression in human malignant gliomas. Cancer Res. 56,164 -171.[Abstract/Free Full Text]

Kinzler, K.W., and Vogelstein, B. (1998) Landscaping the cancer terrain. Science 280,1036 -1037.[Free Full Text]

Kleihues, P., and Ohgaki, H. (1997) Genetics of glioma progression and the definition of primary and secondary glioblastoma. Brain Pathol. 7,1131 -1136.[ISI]

Kleihues, P., Burger, P.C., Plate, K.H., Ohgaki, H., and Cavenee, W.K. (1997) Glioblastoma. In: Kleihues, P., and Cavenee, W.K. (Eds.), Pathology and Genetics of Tumours of the Nervous System. Lyon: International Agency for Research on Cancer, pp.16 -24.

Korkolopoulou, P., Christodoulou, P., Kouzelis, K., Hadjiyannakis, M., Priftis, A., Stamoulis, G., Seretis, A., and Thomas-Tsagli, E. (1997) MDM2 and p53 expression in gliomas: A multivariate survival analysis including proliferation markers and epidermal growth factor receptor. Br. J. Cancer 75,1269 -1278.[ISI][Medline]

Kubo, Y., Urano, Y., Matsumoto, K., Ahsan, K., and Arase, S. (1997) Mutations of the INK4a locus in squamous cell carcinomas of human skin Biochem. Biophys. Res. Commun. 232, 38-41.[CrossRef][ISI][Medline]

Lang, F.F., Miller, D.C., Koslow, M., and Newcomb, E.W. (1994) Pathways leading to glioblastoma multiforme: A molecular analysis of genetic alterations in 65 astrocytic tumors. J. Neurosurg. 81,427 -436.[ISI][Medline]

Lantos, P.L., VandenBerg, S.R., and Kleihues, P. (1996) Tumours of the Nervous System. In: Graham, D.I., and Lantos, P.L. (Eds.), Greenfield's Neuropathology. London: Arnold, pp. 583-879.

Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S.I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., Bigner, S.H., Giovanella, B.C., Ittmann, M., Tycko, B., Hibshoosh, H., Wigler, M.H., and Parsons, R. (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275,1943 -1947.[Abstract/Free Full Text]

Libermann, T.A., Nusbaum, H.R., Razon, N., Kris, R., Lax, I., Soreq, H., Whittle, N., Waterfield, M.D., Ullrich, A., and Schlessinger, J. (1985) Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 313,144 -147.[CrossRef][Medline]

Louis, D.N. (1994) The p53 gene and protein in human brain tumors. J. Neuropathol. Exp. Neurol. 53, 11-21.[ISI][Medline]

Louis, D.N. (1997) A molecular genetic model of astrocytoma histopathology. Brain Pathol. 7, 755-764.[ISI][Medline]

Louis, D.N., and Gusella, J.F. (1995) A tiger behind many doors: Multiple genetic pathways to maligant glioma. Trends Genet. 11,412 -415.[CrossRef][ISI][Medline]

Louis, D.N., von Deimling, A., Chung, R.Y., Rubio, M.P., Whaley, J.M., Eibl, R.H., Ohgaki, H., Wiestler, O.D., Thor, A.D., and Seizinger, B.R. (1993) Comparative study of p53 gene and protein alterations in human astrocytic tumors. J. Neuropathol. Exp. Neurol. 52, 31-38.[ISI][Medline]

Matsumoto, R., Tada, M., Nozaki, M., Zhang, C.L., Sawamura, Y., and Abe, H. (1998) Short alternative splice transcripts of the mdm2 oncogene correlate to malignancy in human astrocytic neoplasms. Cancer Res. 58,609 -613.[Abstract/Free Full Text]

Meyer-Puttlitz, B., Hayashi, Y., Waha, A., Rollbrocker, B., Bostrom, J., Wiestler, O.D., Louis, D.N., Reifenberger, G., and von Deimling, A. (1997) Molecular genetic analysis of giant cell glioblastomas. Am. J. Pathol. 151,853 -857.[Abstract]

Nagane, M., Coufal, F., Lin, H., Bogler, O., Cavenee, W.K., and Huang, H.J.S. (1996) A common mutant epidermal growth factor receptor confers enhanced tumorigenicity on human glioblastoma cells by increasing proliferation and reducing apoptosis. Cancer Res. 56,5079 -5086.[Abstract/Free Full Text]

Nelson, J.S., Tsukada, Y., Schoenfeld, D., Fulling, K., Lamarche, J., and Peress, N. (1983) Necrosis as a prognostic criterion in malignant supratentorial, astrocytic gliomas. Cancer 52,550 -554.[CrossRef][ISI][Medline]

Newcomb, E.W., Madonia, W.J., Pisharody, S., Lang, F.F., Koslow, M., and Miller, D.C. (1993) A correlative study of p53 protein alteration and p53 gene mutation in glioblastoma multiforme. Brain Pathol. 3,229 -235.[ISI][Medline]

Newcomb, E.W., Cohen, H., Lee, S.R., Bhalla, S.K., Bloom, J., Hayes, R.L., and Miller, D.C. (1998) Survival of patients with glioblastoma multiforme is not influenced by altered expression of p16, p53, EGFR, MDM2 or Bcl-2 genes. Brain Pathol. 8, 655-667.[ISI][Medline]

Nigro, J.M., Baker, S.J., Preisinger, A.C., Jessup, J.M., Hostetter, R., Cleary, K., Bigner, S.H., Davidson, N., Baylin, S., Devilee, P., Glover, T., Collins, F.S., Weston, A., Modali, R., Harris, C.C., and Vogelstein, B. (1989) Mutations in the p53 gene occur in diverse human tumour types. Nature 342, 705-708. (Letter)[CrossRef][Medline]

Nishikawa, R., Ji, X.D., Harmon, R.C., Lazar, C.S., Gill, G.N., Cavenee, W.K., and Huang, H.J. (1994) A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc. Natl. Acad. Sci. U. S. A. 91,7727 -7731.[Abstract/Free Full Text]

Ohgaki, H., Schauble, B., zur Hausen, A., von Ammon, K., and Kleihues, P. (1995) Genetic alterations associated with the evolution and progression of astrocytic brain tumours. Virchows Arch. 427,113 -118.[ISI][Medline]

Olson, D.C., Marechal, V., Momand, J., Chen, J., Romocki, C., and Levine, A.J. (1993) Identification and characterization of multiple MDM-2 proteins and MDM-2-p53 protein complexes. Oncogene 8,2353 -2360.[ISI][Medline]

Peraud, A., Watanabe, K., Plate, K.H., Yonekawa, Y., Kleihues, P., and Ohgaki, H. (1997) p53 mutations versus EGF receptor expression in giant cell glioblastomas. J. Neuropath. Exp. Neurol. 56,1236 -1241.[ISI][Medline]

Picksley, S.M., and Lane, D.P. (1993) The p53-mdm2 autoregulatory feedback loop: A paradigm for the regulation of growth control by p53? Bioessays 15,689 -690.[CrossRef][ISI][Medline]

Pomerantz, J., Schreiber-Agus, N., Liegeois, N.J., Silverman, A., Alland, L., Chin, L., Potes, J., Chen, K., Orlow, I., Lee, H.W., Cordon-Cardo, C., and DePinho, R.A. (1998) The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell 92,713 -723.[CrossRef][ISI][Medline]

Prigent, S.A., Nagane, M., Lin, H., Huvar, I., Boss, G.R., Feramisco, J.R., Cavenee, W. K., and Huang, H.S. (1996) Enhanced tumorigenic behavior of glioblastoma cells expressing a truncated epidermal growth factor receptor is mediated through the Ras-Shc-Grb2 pathway. J. Biol. Chem. 271,25639 -25645.[Abstract/Free Full Text]

Rasheed, B.K., McLendon, R.E., Herndon, J.E., Friedman, H.S., Friedman, A.H., Bigner, D.D., and Bigner, S.H. (1994) Alterations of the TP53 gene in human gliomas. Cancer Res. 54,1324 -1330.[Abstract/Free Full Text]

Rasheed, B.K., McLendon, R.E., Friedman, H.S., Friedman, A.H., Fuchs, H.E., Bigner, D.D., and Bigner, S.H. (1995) Chromosome 10 deletion mapping in human gliomas: A common deletion region in 10q25. Oncogene 10,2243 -2246.[ISI][Medline]

Rasheed, B.K.A., Stenzel, T.T., McLendon, R.E., Parsons, R., Friedman, A.H., Friedman, H.S., Bigner, D.D., and Bigner, S.H. (1997) PTEN gene mutations are seen in high-grade but not in low-grade gliomas. Cancer Res. 57,4187 -4190.[Abstract/Free Full Text]

Reifenberger, G., Liu, L., Ichimura, K., Schmidt, E.E., and Collins, V.P. (1993) Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations. Cancer Res. 53,2736 -2739.[Abstract/Free Full Text]

Reifenberger, J., Ring, G.U., Gies, U., Cobbers, L., Oberstrass, J., An, H.X., Niederacher, D., Wechsler, W., and Reifenberger, G. (1996) Analysis of p53 mutation and epidermal growth factor receptor amplification in recurrent gliomas with malignant progression. J. Neuropathol. Exp. Neurol. 55,822 -831.[ISI][Medline]

Reyes-Mugica, M., Rieger-Christ, K., Ohgaki, H., Ekstrand, B.C., Helie, M., Kleinman, G., Yahanda, A., Fearon, E.R., Kleihues, P., and Reale, M.A. (1997) Loss of DCC expression and glioma progression. Cancer Res. 57,382 -386.[Abstract/Free Full Text]

Russell, D.S., and Rubinstein, L.J. (1989)Pathology of Tumours of the Nervous System. Fifth edition . London: Edward Arnold.

Scherer, H.J. (1938) Structural development in gliomas. Am. J. Cancer, 34,333 -351.

———. (1940a) Cerebral astrocytomas and their derivatives. Am. J. Cancer 40,159 -198.

———. (1940b) The forms of growth in gliomas and their practical significance. Brain 63, 1-35.[Free Full Text]

———. (1940c) The pathology of cerebral gliomas. A critical review. J. Neurol. 3, 147-177.

Shiohara, M., Spirin, K., Said, J.W., Gombart, A.F., Nakamaki, T., Takeuchi, S., Hatta, Y., Morosetti, R., Tasaka, T., Seriu, T., Bartram, C., Miller, C.W., Tomonaga, M., and Koef'er, H.P. (1996) Alterations of the cyclin-dependent kinase inhibitor p19 (INK4D) is rare in hematopoietic malignancies. Leukemia 10,1897 -1900.[ISI][Medline]

Sidransky, D., Mikkelsen, T., Schwechheimer, K., Rosenblum, M.L., Cavenee, W.K., and Vogelstein, B. (1992) Clonal expansion of p53 mutant cells is associated with brain tumour progression. Nature, 355,846 -847.[CrossRef][Medline]

Sigalas, I., Calvert, A.H., Anderson, J.J., Neal, D.E., and Lunec, J. (1996) Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: Transforming ability and frequent detection in human cancer. Nat. Med. 2,912 -917.[CrossRef][ISI][Medline]

Sonoda, Y., Murakami, Y., Tominaga, T., Kayama, T., Yoshimoto, T., and Sekiya, T. (1996) Deletion mapping of chromosome 10 in human glioma. Jpn. J. Cancer Res. 87,363 -367.[ISI][Medline]

Steck, P.A., Ligon, A.H., Cheong, P., Yung, W.K., and Pershouse, M.A. (1995) Two tumor suppressive loci on chromosome 10 involved in human glioblastomas. Genes Chromosomes Cancer 12,255 -261.

Steck, P.A., Pershouse, M.A., Jasser, S.A., Yung, W.K. A., Lin, H., Ligon, A.H., Langford, L.A., Baumgard, M.L., Hattier, T., Davis, T., Frye, C., Hu, R., Swedlund, B., Teng, D.H.F., and Tavtigian, S.V. (1997) Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nature Genet. 15,356 -362.[CrossRef][ISI][Medline]

Sugawa, N., Ekstrand, A.J., James, C.D., and Collins, V.P. (1990) Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc. Natl. Acad. Sci. U. S. A. 87,8602 -8606.[Abstract/Free Full Text]

Tohma, Y., Gratas, C., Biernat, W., Peraud, A., Fukuda, M., Yonekawa, Y., Kleihues, P., and Ohgaki, H. (1998a) PTEN (MMAC1) mutations are frequent in primary glioblastomas (de novo) but not in secondary glioblastomas. J. Neuropath. Exp. Neurol. 57,684 -689.[ISI][Medline]

Tohma, Y., Gratas, C., Van Meir, E.G., Desbaillets, I., Tenan, M., Tachibana, O., Kleihues, P., and Ohgaki, H. (1998b) Necrogenesis and Fas/APO-1(CD95) expression in primary (de novo) and secondary glioblastomas. J. Neuropath. Exp. Neurol. 57,239 -245.[ISI][Medline]

Ueki, K., Ono, Y., Henson, J.W., Efird, J.T., von Deimling, A., and Louis, D.N. (1996) CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated. Cancer Res. 56,150 -153.[Abstract/Free Full Text]

van Meyel, D.J., Ramsay, D.A., Casson, A.G., Keeney, M., Chambers, A.F., and Cairncross, J.G. (1994) p53 mutation, expression, and DNA ploidy in evolving gliomas: Evidence for two pathways of progression. J. Natl. Cancer Inst. 86,1011 -1017.[Abstract/Free Full Text]

Vogelstein, B., and Kinzler, K.W. (1993) The multistep nature of cancer. Trends Genet. 9, 138-141.[CrossRef][ISI][Medline]

von Deimling, A., Louis, D.N., von Ammon, K., Petersen, I., Hoell, T., Chung, R.Y., Martuza, R.L., Schoenfeld, D.A., Yasargil, M.G., Wiestler, O.D., and Seizinger, B.R. (1992a) Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme. J. Neurosurg. 77,295 -301.[ISI][Medline]

von Deimling, A., Louis, D.N., von Ammon, K., Petersen, I., Wiestler, O.D., and Seizinger, B.R. (1992b) Evidence for a tumor suppressor gene on chromosome 19q associated with human astrocytomas, oligodendrogliomas, and mixed gliomas. Cancer Res. 52,4277 -4279.[Abstract/Free Full Text]

von Deimling, A., von Ammon, K., Schoenfeld, D., Wiestler, O.D., Seizinger, B.R., and Louis, D.N. (1993) Subsets of glioblastoma multiforme defined by molecular genetic analysis. Brain Pathol. 3,19 -26.[ISI][Medline]

von Deimling, A., Nagel, J., Bender, B., Lenartz, D., Schramm, J., Louis, D.N., and Wiestler, O.D. (1994) Deletion mapping of chromosome 19 in human gliomas. Int. J. Cancer 57,676 -680.[ISI][Medline]

von Deimling, A., Louis, D.N., and Wiestler, O.D. (1995) Molecular pathways in the formation of gliomas. Glia 15,328 -338.[CrossRef][ISI][Medline]

Wang, S.I., Puc, J., Li, J., Bruce, J.N., Cairns, P., Sidransky, D., and Parsons, R. (1997) Somatic mutations of PTEN in glioblastoma multiforme. Cancer Res. 57,4183 -4186.[Abstract/Free Full Text]

Watanabe, K., Tachibana, O., Sato, K., Yonekawa, Y., Kleihues, P., and Ohgaki, H. (1996) Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol. 6, 217-224.[ISI][Medline]

Watanabe, K., Sato, K., Biernat, W., Tachibana, O., von Ammon, K., Ogata, N., Yonekawa, Y., Kleihues, P., and Ohgaki, H. (1997a) Incidence and timing of p53 mutations during astrocytoma progression in patients with multiple biopsies. Clin. Cancer Res. 3, 523-530.[Abstract]

Watanabe, K., Tachibana, O., Yonekawa, Y., Kleihues, P., and Ohgaki, H. (1997b) Role of gemistocytes in astrocytoma progression. Lab. Invest. 76,277 -284.[ISI][Medline]

Winger, M.J., Macdonald, D.R., and Cairncross, J.G. (1989) Supratentorial anaplastic gliomas in adults. The prognostic importance of extent of resection and prior low-grade glioma. J. Neurosurg. 71,487 -493.[ISI][Medline]

Wong, A.J., Ruppert, J.M., Bigner, S.H., Grzeschik, C.H., Humphrey, P.A., Bigner, D. S., and Vogelstein, B. (1992) Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc. Natl. Acad. Sci. U. S. A. 89,2965 -2969.[Abstract/Free Full Text]

Zauberman, A., Flusberg, D., Haupt, Y., Barak, Y., and Oren, M. (1995) A functional p53-responsive intronic promoter is contained within the human mdm2 gene. Nucleic. Acids. Res. 23,2584 -2592.[Abstract/Free Full Text]

Zhang, Y., Xiong, Y., and Yarbrough, W.G. (1998) ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 92,725 -734.[CrossRef][ISI][Medline]

Zulch, K.J. (1986). Brain Tumors. Their Biology and Pathology. Third edition. Berlin, Springer Verlag.




This article has been cited by other articles:


Home page
Am. J. Neuroradiol.Home page
T. Kato, J. Shinoda, N. Oka, K. Miwa, N. Nakayama, H. Yano, T. Maruyama, Y. Muragaki, and T. Iwama
Analysis of 11C-methionine Uptake in Low-Grade Gliomas and Correlation with Proliferative Activity
AJNR Am. J. Neuroradiol., November 1, 2008; 29(10): 1867 - 1871.
[Abstract] [Full Text] [PDF]


Home page
ScienceHome page
D. W. Parsons, S. Jones, X. Zhang, J. C.-H. Lin, R. J. Leary, P. Angenendt, P. Mankoo, H. Carter, I-M. Siu, G. L. Gallia, et al.
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Science, September 26, 2008; 321(5897): 1807 - 1812.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
H. K. Thorarinsdottir, M. Santi, R. McCarter, E. J. Rushing, R. Cornelison, A. Jales, and T. J. MacDonald
Protein Expression of Platelet-Derived Growth Factor Receptor Correlates with Malignant Histology and PTEN with Survival in Childhood Gliomas
Clin. Cancer Res., June 1, 2008; 14(11): 3386 - 3394.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
S. P. Reddy, R. Britto, K. Vinnakota, H. Aparna, H. K. Sreepathi, B. Thota, A. Kumari, B.M. Shilpa, M. Vrinda, S. Umesh, et al.
Novel Glioblastoma Markers with Diagnostic and Prognostic Value Identified through Transcriptome Analysis
Clin. Cancer Res., May 15, 2008; 14(10): 2978 - 2987.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
B. Eun, Y. Lee, S. Hong, J. Kim, H.-W. Lee, K. Kim, W. Sun, and H. Kim
Hes6 Controls Cell Proliferation via Interaction with cAMP-response Element-binding Protein-binding Protein in the Promyelocytic Leukemia Nuclear Body
J. Biol. Chem., February 29, 2008; 283(9): 5939 - 5949.
[Abstract] [Full Text] [PDF]


Home page
BrainHome page
C. S. Jung, C. Foerch, A. Schanzer, A. Heck, K. H. Plate, V. Seifert, H. Steinmetz, A. Raabe, and M. Sitzer
Serum GFAP is a diagnostic marker for glioblastoma multiforme
Brain, December 1, 2007; 130(12): 3336 - 3341.
[Abstract] [Full Text] [PDF]


Home page
Protein Eng Des SelHome page
M. Friedman, E. Nordberg, I. Hoiden-Guthenberg, H. Brismar, G.P. Adams, F.Y. Nilsson, J. Carlsson, and S. Stahl
Phage display selection of Affibody molecules with specific binding to the extracellular domain of the epidermal growth factor receptor
Protein Eng. Des. Sel., April 23, 2007; (2007) gzm011v1.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
M. K. Nicholas, R. V. Lukas, N. F. Jafri, L. Faoro, and R. Salgia
Epidermal Growth Factor Receptor-Mediated Signal Transduction in the Development and Therapy of Gliomas
Clin. Cancer Res., December 15, 2006; 12(24): 7261 - 7270.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
E. A. Maher, C. Brennan, P. Y. Wen, L. Durso, K. L. Ligon, A. Richardson, D. Khatry, B. Feng, R. Sinha, D. N. Louis, et al.
Marked Genomic Differences Characterize Primary and Secondary Glioblastoma Subtypes and Identify Two Distinct Molecular and Clinical Secondary Glioblastoma Entities
Cancer Res., December 1, 2006; 66(23): 11502 - 11513.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
P. O. Sakariassen, L. Prestegarden, J. Wang, K.-O. Skaftnesmo, R. Mahesparan, C. Molthoff, P. Sminia, E. Sundlisaeter, A. Misra, B. B. Tysnes, et al.
Angiogenesis-independent tumor growth mediated by stem-like cancer cells
PNAS, October 31, 2006; 103(44): 16466 - 16471.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
H. Okamoto, J. Li, A. O. Vortmeyer, H. Jaffe, Y.-S. Lee, S. Glasker, T.-S. Sohn, W. Zeng, B. Ikejiri, M. A. Proescholdt, et al.
Comparative proteomic profiles of meningioma subtypes.
Cancer Res., October 15, 2006; 66(20): 10199 - 10204.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
E. I. Fomchenko and E. C. Holland
Mouse models of brain tumors and their applications in preclinical trials.
Clin. Cancer Res., September 15, 2006; 12(18): 5288 - 5297.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
C.-L. Tso, W. A. Freije, A. Day, Z. Chen, B. Merriman, A. Perlina, Y. Lee, E. Q. Dia, K. Yoshimoto, P. S. Mischel, et al.
Distinct Transcription Profiles of Primary and Secondary Glioblastoma Subgroups
Cancer Res., January 1, 2006; 66(1): 159 - 167.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
B. M. Woerner, N. M. Warrington, A. L. Kung, A. Perry, and J. B. Rubin
Widespread CXCR4 Activation in Astrocytomas Revealed by Phospho-CXCR4-Specific Antibodies
Cancer Res., December 15, 2005; 65(24): 11392 - 11399.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
A. B. Lassman, M. R. Rossi, J. R. Razier, L. E. Abrey, F. S. Lieberman, C. N. Grefe, K. Lamborn, W. Pao, A. H. Shih, J. G. Kuhn, et al.
Molecular Study of Malignant Gliomas Treated with Epidermal Growth Factor Receptor Inhibitors: Tissue Analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01
Clin. Cancer Res., November 1, 2005; 11(21): 7841 - 7850.
[Abstract] [Full Text] [PDF]


Home page
Neuro OncolHome page
S. M. Chang, S. L. Reynolds, N. Butowski, K. R. Lamborn, J. C. Buckner, R. S. Kaplan, and D. D. Bigner
GNOSIS: Guidelines for neuro-oncology: Standards for investigational studies--reporting of phase 1 and phase 2 clinical trials
Neuro-oncol, October 1, 2005; 7(4): 425 - 434.
[Abstract] [PDF]


Home page
Cancer Res.Home page
S. L. Holmen and B. O. Williams
Essential Role for Ras Signaling in Glioblastoma Maintenance
Cancer Res., September 15, 2005; 65(18): 8250 - 8255.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
J. N. Rich, C. Hans, B. Jones, E. S. Iversen, R. E. McLendon, B.K. A. Rasheed, A. Dobra, H. K. Dressman, D. D. Bigner, J. R. Nevins, et al.
Gene Expression Profiling and Genetic Markers in Glioblastoma Survival
Cancer Res., May 15, 2005; 65(10): 4051 - 4058.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
A. Misra, M. Pellarin, J. Nigro, I. Smirnov, D. Moore, K. R. Lamborn, D. Pinkel, D. G. Albertson, and B. G. Feuerstein
Array Comparative Genomic Hybridization Identifies Genetic Subgroups in Grade 4 Human Astrocytoma
Clin. Cancer Res., April 15, 2005; 11(8): 2907 - 2918.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
F. Lefranc, J. Brotchi, and R. Kiss
Possible Future Issues in the Treatment of Glioblastomas: Special Emphasis on Cell Migration and the Resistance of Migrating Glioblastoma Cells to Apoptosis
J. Clin. Oncol., April 1, 2005; 23(10): 2411 - 2422.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
J. Schwartzbaum, F. Jonsson, A. Ahlbom, S. Preston-Martin, B. Malmer, S. Lonn, K. Soderberg, and M. Feychting
Prior Hospitalization for Epilepsy, Diabetes, and Stroke and Subsequent Glioma and Meningioma Risk
Cancer Epidemiol. Biomarkers Prev., March 1, 2005; 14(3): 643 - 650.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
A. B. Heimberger, E. C. McGary, D. Suki, M. Ruiz, H. Wang, G. N. Fuller, and M. Bar-Eli
Loss of the AP-2{alpha} Transcription Factor Is Associated with the Grade of Human Gliomas
Clin. Cancer Res., January 1, 2005; 11(1): 267 - 272.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
T. Kodama, E. Ikeda, A. Okada, T. Ohtsuka, M. Shimoda, T. Shiomi, K. Yoshida, M. Nakada, E. Ohuchi, and Y. Okada
ADAM12 Is Selectively Overexpressed in Human Glioblastomas and Is Associated with Glioblastoma Cell Proliferation and Shedding of Heparin-Binding Epidermal Growth Factor
Am. J. Pathol., November 1, 2004; 165(5): 1743 - 1753.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
L. W. Kracht, H. Miletic, S. Busch, A. H. Jacobs, J. Voges, M. Hoevels, J. C. Klein, K. Herholz, and W.-D. Heiss
Delineation of Brain Tumor Extent with [11C]L-Methionine Positron Emission Tomography: Local Comparison with Stereotactic Histopathology
Clin. Cancer Res., November 1, 2004; 10(21): 7163 - 7170.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
G. S. Kapoor, D. Kapitonov, and D. M. O'Rourke
Transcriptional Regulation of Signal Regulatory Protein {alpha}1 Inhibitory Receptors by Epidermal Growth Factor Receptor Signaling
Cancer Res., September 15, 2004; 64(18): 6444 - 6452.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
D. K. Broderick, C. Di, T. J. Parrett, Y. R. Samuels, J. M. Cummins, R. E. McLendon, D. W. Fults, V. E. Velculescu, D. D. Bigner, and H. Yan
Mutations of PIK3CA in Anaplastic Oligodendrogliomas, High-Grade Astrocytomas, and Medulloblastomas
Cancer Res., August 1, 2004; 64(15): 5048 - 5050.
[Abstract] [Full Text] [PDF]


Home page
J. Neurol. Neurosurg. PsychiatryHome page
T J M Hulsebos, D Troost, and S Leenstra
Molecular-genetic characterisation of gliomas that recur as same grade or higher grade tumours
J. Neurol. Neurosurg. Psychiatry, May 1, 2004; 75(5): 723 - 726.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
C. Walker, D. G. du Plessis, K. A. Joyce, Y. Machell, J. Thomson-Hehir, S. A. Al Haddad, J. C. Broome, and P. C. Warnke
Phenotype versus Genotype in Gliomas Displaying Inter- or Intratumoral Histological Heterogeneity
Clin. Cancer Res., October 15, 2003; 9(13): 4841 - 4851.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
T. Watanabe, Y. Katayama, A. Yoshino, C. Komine, and T. Yokoyama
Deregulation of the TP53/p14ARF Tumor Suppressor Pathway in Low-Grade Diffuse Astrocytomas and Its Influence on Clinical Course
Clin. Cancer Res., October 15, 2003; 9(13): 4884 - 4890.
[Abstract] [Full Text] [PDF]


Home page
Neuro OncolHome page
K. Tada, M. Kochi, H. Saya, J.-i. Kuratsu, S. Shiraishi, T. Kamiryo, N. Shinojima, and Y. Ushio
Preliminary observations on genetic alterations in pilocytic astrocytomas associated with neurofibromatosis 1
Neuro-oncol, October 1, 2003; 5(4): 228 - 234.
[Abstract] [PDF]


Home page
Am. J. Pathol.Home page
J. van den Boom, M. Wolter, R. Kuick, D. E. Misek, A. S. Youkilis, D. S. Wechsler, C. Sommer, G. Reifenberger, and S. M. Hanash
Characterization of Gene Expression Profiles Associated with Glioma Progression Using Oligonucleotide-Based Microarray Analysis and Real-Time Reverse Transcription-Polymerase Chain Reaction
Am. J. Pathol., September 1, 2003; 163(3): 1033 - 1043.
[Abstract] [Full Text] [PDF]


Home page
J. Neurol. Neurosurg. PsychiatryHome page
A M Stark, P Witzel, R J Strege, H-H Hugo, and H M Mehdorn
p53, mdm2, EGFR, and msh2 expression in paired initial and recurrent glioblastoma multiforme
J. Neurol. Neurosurg. Psychiatry, June 1, 2003; 74(6): 779 - 783.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
T. Abe, K. Terada, H. Wakimoto, R. Inoue, E. Tyminski, R. Bookstein, J. P. Basilion, and E. A. Chiocca
PTEN Decreases in Vivo Vascularization of Experimental Gliomas in Spite of Proangiogenic Stimuli
Cancer Res., May 1, 2003; 63(9): 2300 - 2305.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
A. Giese, R. Bjerkvig, M.E. Berens, and M. Westphal
Cost of Migration: Invasion of Malignant Gliomas and Implications for Treatment
J. Clin. Oncol., April 15, 2003; 21(8): 1624 - 1636.
[Abstract] [Full Text] [PDF]


Home page
Neuro OncolHome page
S. Ueda, T. Mineta, K. Suzuyama, M. Furuta, T. Shiraishi, and K. Tabuchi
Biologic characterization of a secondary glioblastoma with extracranial progression and systemic metastasis
Neuro-oncol, January 1, 2003; 5(1): 14 - 18.
[Abstract] [PDF]


Home page
Am. J. Pathol.Home page
M. Bacher, J. Schrader, N. Thompson, K. Kuschela, D. Gemsa, G. Waeber, and J. Schlegel
Up-Regulation of Macrophage Migration Inhibitory Factor Gene and Protein Expression in Glial Tumor Cells during Hypoxic and Hypoglycemic Stress Indicates a Critical Role for Angiogenesis in Glioblastoma Multiforme
Am. J. Pathol., January 1, 2003; 162(1): 11 - 17.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
L. Uhrbom, C. Dai, J. C. Celestino, M. K. Rosenblum, G. N. F